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Article ; Online: Nutrition and Food Security among Veterans: Operationalizing 'Nutritional Functioning'.

Brostow, Diana P / Smith, Alexandra A / Bahraini, Nazanin H / Besterman-Dahan, Karen / Forster, Jeri E / Brenner, Lisa A

Archives of physical medicine and rehabilitation

2024

Abstract: Objective: To assess injured military veterans' experiences, beliefs and daily physical and psychosocial functioning in relation to food and nutrition.: Design: We used a convergent mixed-methods study design, and the International Classification of ... ...

Abstract	Objective: To assess injured military veterans' experiences, beliefs and daily physical and psychosocial functioning in relation to food and nutrition. Design: We used a convergent mixed-methods study design, and the International Classification of Functioning, Disability and Health to operationalize the core constructs and influencing factors related to physical and psychosocial functioning, and food and nutrition. Setting: Three Veterans Affairs Polytrauma Rehabilitation Centers. Participants: Veterans who served in the United States military on or after September 11 Intervention: None MAIN OUTCOME MEASURES: Themes from survey responses and semi-structured interview data were pooled into core constructs, and influencing factors. Results: 37 veterans completed all surveys and participated in recorded interviews. Based on qualitative and quantitative data, veterans' relation to food and nutrition (i.e., nutritional functioning) was found to be characterized by 5 core constructs, including food background, nutrition knowledge, meal aptitude, resource navigation, and navigation to/of food spaces. Nutritional functioning was found to be shaped by 5 influencing factors, including injuries and health conditions, ideological and cultural exposures, relationships, and current beliefs and behaviors. Conclusions: Nutritional functioning (food background, nutrition knowledge, meal aptitude, resource navigation, and navigation to/of food spaces) among injured veterans is complex, and shaped by multiple physical, psychosocial, economic, and cultural factors.
Language	English
Publishing date	2024-04-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	80057-0
ISSN	1532-821X ; 0003-9993
ISSN (online)	1532-821X
ISSN	0003-9993
DOI	10.1016/j.apmr.2024.04.006
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Article: Food Insecurity and Food Worries During the COVID-19 Pandemic: A Point-In-Time Study of Injured United States Veterans.

Brostow, Diana P / Smith, Alexandra A / Bahraini, Nazanin H / Besterman-Dahan, Karen / Forster, Jeri E / Brenner, Lisa A

Journal of hunger & environmental nutrition

2022 Volume 17

Abstract: US Military Veterans experience higher rates of food insecurity compared to civilians, but the impact of the COVID-19 pandemic on Veterans is unclear. We conducted a nationwide survey of injured post-9/11 Veterans' food security, Coronavirus exposure, ... ...

Abstract	US Military Veterans experience higher rates of food insecurity compared to civilians, but the impact of the COVID-19 pandemic on Veterans is unclear. We conducted a nationwide survey of injured post-9/11 Veterans' food security, Coronavirus exposure, and nutrition habits. Of 193 Veterans, 63 (32.6%) were food insecure. Food insecurity was associated with Hispanic ethnicity (
Language	English
Publishing date	2022-09-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	2251933-6
ISSN	1932-0256 ; 1932-0248
ISSN (online)	1932-0256
ISSN	1932-0248
DOI	10.1080/19320248.2022.2118564
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Article ; Online: Child Health Care in Israel.

Tasher, Diana / Rubin, Lisa / Grossman, Zachi / Grotto, Itamar / Dahan, Dikla / Berlowitz, Yitzhak / Somekh, Eli

The Journal of pediatrics

2016 Volume 177S, Page(s) S107–S115

Abstract: Israel is a relatively rapidly growing country with a high fertility rate and a young population. These data emphasize the importance of an efficient and appropriate pediatric service for its population. Although the pediatric service in Israel has ... ...

Abstract	Israel is a relatively rapidly growing country with a high fertility rate and a young population. These data emphasize the importance of an efficient and appropriate pediatric service for its population. Although the pediatric service in Israel has attained several achievements, such as a relatively low infant mortality, high vaccination rates, and a primary care service that is mainly based on licensed pediatricians, several challenges, such as overcoming inequalities in health care and health indices between different regions and different populations within the country and the provision of a more organized mental and dental health care service to children, need to be addressed.
MeSH term(s)	Child ; Child Health ; Child Health Services ; Child, Preschool ; Humans ; Israel
Language	English
Publishing date	2016-09-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3102-1
ISSN	1097-6833 ; 0022-3476
ISSN (online)	1097-6833
ISSN	0022-3476
DOI	10.1016/j.jpeds.2016.04.047
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Article ; Online: Expression of microRNAs is essential for arterial myogenic tone and pressure-induced activation of the PI3-kinase/Akt pathway.

Bhattachariya, Anirban / Dahan, Diana / Turczyńska, Karolina M / Swärd, Karl / Hellstrand, Per / Albinsson, Sebastian

Cardiovascular research

2014 Volume 101, Issue 2, Page(s) 288–296

Abstract: Aims: The myogenic response is the intrinsic ability of small arteries to constrict in response to increased intraluminal pressure. Although microRNAs have been shown to play a role in vascular smooth muscle function, their importance in the regulation ... ...

Abstract	Aims: The myogenic response is the intrinsic ability of small arteries to constrict in response to increased intraluminal pressure. Although microRNAs have been shown to play a role in vascular smooth muscle function, their importance in the regulation of the myogenic response is not known. In this study, we investigate the role of microRNAs in the regulation of myogenic tone by using smooth muscle-specific and tamoxifen-inducible deletion of the endonuclease Dicer in mice. Methods and results: In order to avoid effects of Dicer deletion on smooth muscle differentiation and growth, we used an early time point (5 weeks) after the tamoxifen-induction of Dicer knockout (KO). At this time point, we found that myogenic tone was completely absent in the mesenteric arteries of Dicer KO mice. This was associated with a reduced pressure-induced Akt-phosphorylation, possibly via increased phosphatase and tensin homologue (PTEN) expression, which was found to be a target of miR-26a. Furthermore, loss of myogenic tone was associated with a decreased depolarization-induced calcium influx, and was restored by the L-type channel agonist Bay K 8644 or by transient stimulation with angiotensin II (Ang II). The effect of Ang II was dependent on AT1-receptors and activation of the PI3-kinase/Akt pathway. Conclusion: In this study we have identified novel mechanisms that regulate myogenic tone in resistance arteries, which involves microRNA-dependent control of PI3-kinase/Akt signalling and L-type calcium influx. Furthermore, we have demonstrated that transient stimulation by Ang II can have long-lasting effects by potentiating myogenic tone.
MeSH term(s)	Animals ; Arterial Pressure ; Calcium Channel Agonists/pharmacology ; Calcium Channels, L-Type/metabolism ; Calcium Signaling ; Cells, Cultured ; DEAD-box RNA Helicases/deficiency ; DEAD-box RNA Helicases/genetics ; Enzyme Activation ; Genotype ; Mechanotransduction, Cellular/drug effects ; Mesenteric Arteries/enzymology ; Mice ; Mice, Knockout ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/enzymology ; PTEN Phosphohydrolase/metabolism ; Phenotype ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Renin-Angiotensin System ; Ribonuclease III/deficiency ; Ribonuclease III/genetics ; Time Factors ; Transfection ; Vasoconstriction/drug effects ; Vasodilation/drug effects
Chemical Substances	Calcium Channel Agonists ; Calcium Channels, L-Type ; MicroRNAs ; Mirn26 microRNA, mouse ; Phosphatidylinositol 3-Kinase (EC 2.7.1.137) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Dicer1 protein, mouse (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3) ; PTEN Phosphohydrolase (EC 3.1.3.67) ; Pten protein, mouse (EC 3.1.3.67) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2014-02-01
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80340-6
ISSN	1755-3245 ; 0008-6363
ISSN (online)	1755-3245
ISSN	0008-6363
DOI	10.1093/cvr/cvt253
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Article ; Online: Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.

Ekman, Mari / Bhattachariya, Anirban / Dahan, Diana / Uvelius, Bengt / Albinsson, Sebastian / Swärd, Karl

PloS one

2013 Volume 8, Issue 12, Page(s) e82308

Abstract: Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower ... ...

Abstract	Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness. c-Myc, NF-κB and SMAD3, all of which repress miR-29, were activated in the rat detrusor following partial bladder outlet obstruction but at different times. c-Myc and NF-κB activation occurred early after obstruction, and SMAD3 phosphorylation increased later, with a significant elevation at 6 weeks. c-Myc, NF-κB and SMAD3 activation, respectively, correlated with repression of miR-29b and miR-29c at 10 days of obstruction and with repression of miR-29c at 6 weeks. An mRNA microarray analysis showed that the reduction of miR-29 following outlet obstruction was associated with increased levels of miR-29 target mRNAs, including mRNAs for tropoelastin, the matricellular protein Sparc and collagen IV. Outlet obstruction increased protein levels of eight out of eight examined miR-29 targets, including tropoelastin and Sparc. Transfection of human bladder smooth muscle cells with antimiR-29c and miR-29c mimic caused reciprocal changes in target protein levels in vitro. Tamoxifen inducible and smooth muscle-specific deletion of Dicer in mice reduced miR-29 expression and increased tropoelastin and the thickness of the basal lamina surrounding smooth muscle cells in the bladder. It also increased detrusor stiffness independent of outlet obstruction. Taken together, our study supports a model where the combined repressive influences of c-Myc, NF-κB and SMAD3 reduce miR-29 in bladder outlet obstruction, and where the resulting drop in miR-29 contributes to matrix remodeling and altered passive mechanical properties of the detrusor.
MeSH term(s)	Animals ; Extracellular Matrix/genetics ; Extracellular Matrix/metabolism ; Extracellular Matrix/pathology ; Humans ; Male ; Mice ; MicroRNAs/biosynthesis ; MicroRNAs/genetics ; NF-kappa B/genetics ; NF-kappa B/metabolism ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Rats ; Smad3 Protein/genetics ; Smad3 Protein/metabolism ; Urinary Bladder Neck Obstruction/genetics ; Urinary Bladder Neck Obstruction/metabolism ; Urinary Bladder Neck Obstruction/pathology
Chemical Substances	MIRN200 microRNA, rat ; MIRN29 microRNA, mouse ; MIRN29a microRNA, human ; MYC protein, human ; MicroRNAs ; Myc protein, mouse ; NF-kappa B ; Proto-Oncogene Proteins c-myc ; SMAD3 protein, human ; Smad3 Protein ; Smad3 protein, mouse ; Smad3 protein, rat
Language	English
Publishing date	2013-12-10
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0082308
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Article ; Online: Implication of the ryanodine receptor in TRPV4-induced calcium response in pulmonary arterial smooth muscle cells from normoxic and chronically hypoxic rats.

Dahan, Diana / Ducret, Thomas / Quignard, Jean-François / Marthan, Roger / Savineau, Jean-Pierre / Estève, Eric

American journal of physiology. Lung cellular and molecular physiology

2012 Volume 303, Issue 9, Page(s) L824–33

Abstract: There is a growing body of evidence indicating that transient receptor potential (TRP) channels are implicated in calcium signaling and various cellular functions in the pulmonary vasculature. The aim of this study was to investigate the expression, ... ...

Abstract	There is a growing body of evidence indicating that transient receptor potential (TRP) channels are implicated in calcium signaling and various cellular functions in the pulmonary vasculature. The aim of this study was to investigate the expression, functional role, and coupling to reticulum calcium channels of the type 4 vanilloid TRP subfamily (TRPV4) in the pulmonary artery from both normoxic (Nx) and chronically hypoxic (CH) rats. Activation of TRPV4 with the specific agonist 4α-phorbol-12,13-didecanoate (4α-PDD, 5 μM) increased the intracellular calcium concentration ([Ca(2+)](i)). This effect was significantly reduced by a high concentration of ryanodine (100 μM) or chronic caffeine (5 mM) that blocked ryanodine receptor (RyR) but was insensitive to xestospongin C (10 μM), an inositol trisphosphate receptor antagonist. Inhibition of RyR1 and RyR3 only with 10 μM of dantrolene did not attenuate the 4α-PDD-induced [Ca(2+)](i) increase. Western blotting experiments revealed the expression of TRPV4 and RyR2 with an increase in both receptors in pulmonary arteries from CH rats vs. Nx rats. Accordingly, the 4α-PDD-activated current, measured with patch-clamp technique, was increased in pulmonary artery smooth muscle cells (PASMC) from CH rats vs. Nx rats. 4α-PDD increased isometric tension in artery rings, and this response was also potentiated under chronic hypoxia conditions. 4α-PDD-induced calcium response, current, and contraction were all inhibited by the selective TRPV4 blocker HC-067047. Collectively, our findings provide evidence of the interplay between TRPV4 and RyR2 in the Ca(2+) release mechanism and contraction in PASMC. This study provides new insights onto the complex calcium signaling in PASMC and point out the importance of the TRPV4-RyR2 signaling pathway under hypoxic conditions that may lead to pulmonary hypertension.
MeSH term(s)	Animals ; Caffeine/pharmacology ; Calcium Channel Agonists/pharmacology ; Calcium Signaling ; Cell Hypoxia ; Cells, Cultured ; Dantrolene/pharmacology ; Hypertension, Pulmonary/etiology ; Hypertension, Pulmonary/metabolism ; Hypoxia/complications ; Hypoxia/metabolism ; In Vitro Techniques ; Macrocyclic Compounds/pharmacology ; Male ; Morpholines/pharmacology ; Muscle Contraction/drug effects ; Muscle Relaxants, Central/pharmacology ; Myocytes, Smooth Muscle/metabolism ; Oxazoles/pharmacology ; Patch-Clamp Techniques ; Phorbols/pharmacology ; Pulmonary Artery/pathology ; Pulmonary Artery/physiopathology ; Pyrroles/pharmacology ; Rats ; Rats, Wistar ; Ryanodine/pharmacology ; Ryanodine Receptor Calcium Release Channel/metabolism ; TRPV Cation Channels/agonists ; TRPV Cation Channels/antagonists & inhibitors ; TRPV Cation Channels/metabolism
Chemical Substances	Calcium Channel Agonists ; HC-067047 ; Macrocyclic Compounds ; Morpholines ; Muscle Relaxants, Central ; Oxazoles ; Phorbols ; Pyrroles ; Ryanodine Receptor Calcium Release Channel ; TRPV Cation Channels ; Trpv4 protein, rat ; xestospongin C ; Ryanodine (15662-33-6) ; Caffeine (3G6A5W338E) ; Dantrolene (F64QU97QCR)
Language	English
Publishing date	2012-09-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1013184-x
ISSN	1522-1504 ; 1040-0605
ISSN (online)	1522-1504
ISSN	1040-0605
DOI	10.1152/ajplung.00244.2011
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Article ; Online: Loss of Vascular Myogenic Tone in miR-143/145 Knockout Mice Is Associated With Hypertension-Induced Vascular Lesions in Small Mesenteric Arteries.

Holmberg, Johan / Bhattachariya, Anirban / Alajbegovic, Azra / Rippe, Catarina / Ekman, Mari / Dahan, Diana / Hien, Tran Thi / Boettger, Thomas / Braun, Thomas / Swärd, Karl / Hellstrand, Per / Albinsson, Sebastian

Arteriosclerosis, thrombosis, and vascular biology

2017 Volume 38, Issue 2, Page(s) 414–424

Abstract: Objective: Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but ... ...

Abstract	Objective: Pressure-induced myogenic tone is involved in autoregulation of local blood flow and confers protection against excessive pressure levels in small arteries and capillaries. Myogenic tone is dependent on smooth muscle microRNAs (miRNAs), but the identity of these miRNAs is unclear. Furthermore, the consequences of altered myogenic tone for hypertension-induced damage to small arteries are not well understood. Approach and results: The importance of smooth muscle-enriched microRNAs, miR-143/145, for myogenic tone was evaluated in miR-143/145 knockout mice. Furthermore, hypertension-induced vascular injury was evaluated in mesenteric arteries in vivo after angiotensin II infusion. Myogenic tone was abolished in miR-143/145 knockout mesenteric arteries, whereas contraction in response to calyculin A and potassium chloride was reduced by ≈30%. Furthermore, myogenic responsiveness was potentiated by angiotensin II in wild-type but not in knockout mice. Angiotensin II administration in vivo elevated systemic blood pressure in both genotypes. Hypertensive knockout mice developed severe vascular lesions characterized by vascular inflammation, adventitial fibrosis, and neointimal hyperplasia in small mesenteric arteries. This was associated with depolymerization of actin filaments and fragmentation of the elastic laminae at the sites of vascular lesions. Conclusions: This study demonstrates that miR-143/145 expression is essential for myogenic responsiveness. During hypertension, loss of myogenic tone results in potentially damaging levels of mechanical stress and detrimental effects on small arteries. The results presented herein provide novel insights into the pathogenesis of vascular disease and emphasize the importance of controlling mechanical factors to maintain structural integrity of the vascular wall.
MeSH term(s)	Actin Cytoskeleton/metabolism ; Actin Cytoskeleton/pathology ; Angiotensin II ; Animals ; Arterial Pressure ; Calcium Signaling ; Cells, Cultured ; Disease Models, Animal ; Elastic Tissue/metabolism ; Elastic Tissue/pathology ; Female ; Fibrosis ; Gene Knockout Techniques ; Hyperplasia ; Hypertension/genetics ; Hypertension/metabolism ; Hypertension/pathology ; Hypertension/physiopathology ; Male ; Mesenteric Arteries/metabolism ; Mesenteric Arteries/pathology ; Mesenteric Arteries/physiopathology ; Mice, Knockout ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/pathology ; Muscle, Smooth, Vascular/physiopathology ; Neointima ; Vascular Remodeling ; Vascular Resistance ; Vasoconstriction
Chemical Substances	MIRN145a microRNA, mouse ; MicroRNAs ; MIRN143 microRNA, mouse ; Angiotensin II (11128-99-7)
Language	English
Publishing date	2017-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1221433-4
ISSN	1524-4636 ; 1079-5642
ISSN (online)	1524-4636
ISSN	1079-5642
DOI	10.1161/ATVBAHA.117.310499
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Article ; Online: MicroRNA-Dependent Control of Serotonin-Induced Pulmonary Arterial Contraction.

Dahan, Diana / Hien, Tran Thi / Tannenberg, Philip / Ekman, Mari / Rippe, Catarina / Boettger, Thomas / Braun, Thomas / Tran-Lundmark, Karin / Tran, Phan-Kiet / Swärd, Karl / Albinsson, Sebastian

Journal of vascular research

2017 Volume 54, Issue 4, Page(s) 246–256

Abstract: Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were ... ...

Abstract	Background: Serotonin (5-HT) is considered to play a role in pulmonary arterial hypertension by regulating vascular remodeling and smooth muscle contractility. Here, arteries from mice with inducible and smooth muscle-specific deletion of Dicer were used to address mechanisms by which microRNAs control 5-HT-induced contraction. Methods: Mice were used 5 weeks after Dicer deletion, and pulmonary artery contractility was analyzed by wire myography. Results: No change was seen in right ventricular systolic pressure following dicer deletion, but systemic blood pressure was reduced. Enhanced 5-HT-induced contraction in Dicer KO pulmonary arteries was associated with increased 5-HT2A receptor mRNA expression whereas 5-HT1B and 5-HT2B receptor mRNAs were unchanged. Contraction by the 5-HT2A agonist TCB-2 was increased in Dicer KO as was the response to the 5-HT2B agonist BW723C86. Effects of Src and protein kinase C inhibition were similar in control and KO arteries, but the effect of inhibition of Rho kinase was reduced. We identified miR-30c as a potential candidate for 5-HT2A receptor regulation as it repressed 5-HT2A mRNA and protein. Conclusion: Our findings show that 5-HT receptor signaling in the arterial wall is subject to regulation by microRNAs and that this entails altered 5-HT2A receptor expression and signaling.
MeSH term(s)	Animals ; Cells, Cultured ; DEAD-box RNA Helicases/deficiency ; DEAD-box RNA Helicases/genetics ; Dose-Response Relationship, Drug ; Gene Expression Regulation ; Genotype ; Male ; Mice, Knockout ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Myography ; Phenotype ; Protein Kinase C/metabolism ; Pulmonary Artery/drug effects ; Pulmonary Artery/metabolism ; Receptor, Serotonin, 5-HT2A/drug effects ; Receptor, Serotonin, 5-HT2A/genetics ; Receptor, Serotonin, 5-HT2A/metabolism ; Ribonuclease III/deficiency ; Ribonuclease III/genetics ; Serotonin/pharmacology ; Signal Transduction/drug effects ; Transfection ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology ; rho-Associated Kinases/metabolism ; src-Family Kinases/metabolism
Chemical Substances	MicroRNAs ; Receptor, Serotonin, 5-HT2A ; Vasoconstrictor Agents ; Serotonin (333DO1RDJY) ; src-Family Kinases (EC 2.7.10.2) ; rho-Associated Kinases (EC 2.7.11.1) ; Protein Kinase C (EC 2.7.11.13) ; Dicer1 protein, mouse (EC 3.1.26.3) ; Ribonuclease III (EC 3.1.26.3) ; DEAD-box RNA Helicases (EC 3.6.4.13)
Language	English
Publishing date	2017
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1105259-4
ISSN	1423-0135 ; 1018-1172
ISSN (online)	1423-0135
ISSN	1018-1172
DOI	10.1159/000478013
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Article ; Online: Mir-29 repression in bladder outlet obstruction contributes to matrix remodeling and altered stiffness.

Mari Ekman / Anirban Bhattachariya / Diana Dahan / Bengt Uvelius / Sebastian Albinsson / Karl Swärd

PLoS ONE, Vol 8, Iss 12, p e

2013 Volume 82308

Abstract	Recent work has uncovered a role of the microRNA (miRNA) miR-29 in remodeling of the extracellular matrix. Partial bladder outlet obstruction is a prevalent condition in older men with prostate enlargement that leads to matrix synthesis in the lower urinary tract and increases bladder stiffness. Here we tested the hypothesis that miR-29 is repressed in the bladder in outlet obstruction and that this has an impact on protein synthesis and matrix remodeling leading to increased bladder stiffness. c-Myc, NF-κB and SMAD3, all of which repress miR-29, were activated in the rat detrusor following partial bladder outlet obstruction but at different times. c-Myc and NF-κB activation occurred early after obstruction, and SMAD3 phosphorylation increased later, with a significant elevation at 6 weeks. c-Myc, NF-κB and SMAD3 activation, respectively, correlated with repression of miR-29b and miR-29c at 10 days of obstruction and with repression of miR-29c at 6 weeks. An mRNA microarray analysis showed that the reduction of miR-29 following outlet obstruction was associated with increased levels of miR-29 target mRNAs, including mRNAs for tropoelastin, the matricellular protein Sparc and collagen IV. Outlet obstruction increased protein levels of eight out of eight examined miR-29 targets, including tropoelastin and Sparc. Transfection of human bladder smooth muscle cells with antimiR-29c and miR-29c mimic caused reciprocal changes in target protein levels in vitro. Tamoxifen inducible and smooth muscle-specific deletion of Dicer in mice reduced miR-29 expression and increased tropoelastin and the thickness of the basal lamina surrounding smooth muscle cells in the bladder. It also increased detrusor stiffness independent of outlet obstruction. Taken together, our study supports a model where the combined repressive influences of c-Myc, NF-κB and SMAD3 reduce miR-29 in bladder outlet obstruction, and where the resulting drop in miR-29 contributes to matrix remodeling and altered passive mechanical properties of the detrusor.
Keywords	Medicine ; R ; Science ; Q
Subject code	500
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Induction of angiotensin-converting enzyme after miR-143/145 deletion is critical for impaired smooth muscle contractility.

Dahan, Diana / Ekman, Mari / Larsson-Callerfelt, Anna-Karin / Turczyńska, Karolina / Boettger, Thomas / Braun, Thomas / Swärd, Karl / Albinsson, Sebastian

American journal of physiology. Cell physiology

2014 Volume 307, Issue 12, Page(s) C1093–101

Abstract: MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and ...

Abstract	MicroRNAs have emerged as regulators of smooth muscle cell phenotype with a role in smooth muscle-related disease. Studies have shown that miR-143 and miR-145 are the most highly expressed microRNAs in smooth muscle cells, controlling differentiation and function. The effect of miR-143/145 knockout has been established in the vasculature but not in smooth muscle from other organs. Using knockout mice we found that maximal contraction induced by either depolarization or phosphatase inhibition was reduced in vascular and airway smooth muscle but maintained in the urinary bladder. Furthermore, a reduction of media thickness and reduced expression of differentiation markers was seen in the aorta but not in the bladder. Supporting the view that phenotype switching depends on a tissue-specific target of miR-143/145, we found induction of angiotensin-converting enzyme in the aorta but not in the bladder where angiotensin-converting enzyme was expressed at a low level. Chronic treatment with angiotensin type-1 receptor antagonist restored contractility in miR-143/145-deficient aorta while leaving bladder contractility unaffected. This shows that tissue-specific targets are critical for the effects of miR-143/145 on smooth muscle differentiation and that angiotensin converting enzyme is one such target.
MeSH term(s)	Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Aorta/drug effects ; Aorta/enzymology ; Aorta/physiopathology ; Dose-Response Relationship, Drug ; Enzyme Induction ; Gene Deletion ; Genotype ; Mice, Knockout ; MicroRNAs/genetics ; MicroRNAs/metabolism ; Muscle Contraction/drug effects ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/enzymology ; Muscle, Smooth, Vascular/physiopathology ; Organ Culture Techniques ; Peptidyl-Dipeptidase A/biosynthesis ; Peptidyl-Dipeptidase A/genetics ; Phenotype ; Respiratory System/enzymology ; Respiratory System/physiopathology ; Signal Transduction ; Urinary Bladder/enzymology ; Urinary Bladder/physiopathology ; Vasoconstriction/drug effects ; Vasoconstrictor Agents/pharmacology
Chemical Substances	Angiotensin II Type 1 Receptor Blockers ; MIRN145a microRNA, mouse ; MicroRNAs ; MIRN143 microRNA, mouse ; Vasoconstrictor Agents ; Peptidyl-Dipeptidase A (EC 3.4.15.1)
Language	English
Publishing date	2014-10-01
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392098-7
ISSN	1522-1563 ; 0363-6143
ISSN (online)	1522-1563
ISSN	0363-6143
DOI	10.1152/ajpcell.00250.2014
Database	MEDical Literature Analysis and Retrieval System OnLINE

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