LIVIVO - Search results -

Search results

Result 1 - 10 of total 92

Search options

Article ; Online: Stellar science: Basic science has lift off!

Persaud, Shanta J / Hills, Claire E

Diabetic medicine : a journal of the British Diabetic Association

2022 Volume 39, Issue 12, Page(s) e14990

MeSH term(s)	Humans ; Periodicals as Topic ; Science ; Diabetes Mellitus
Language	English
Publishing date	2022-11-15
Publishing country	England
Document type	Editorial
ZDB-ID	605769-x
ISSN	1464-5491 ; 0742-3071 ; 1466-5468
ISSN (online)	1464-5491
ISSN	0742-3071 ; 1466-5468
DOI	10.1111/dme.14990
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1954: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Details ▾

Article ; Online: Blocking connexin 43 hemichannel-mediated ATP release reduces communication within and between tubular epithelial cells and medullary fibroblasts in a model of diabetic nephropathy.

Williams, Bethany M / Cliff, Chelsy L / Demirel, Isak / Squires, Paul E / Hills, Claire E

Diabetic medicine : a journal of the British Diabetic Association

2022 Volume 39, Issue 12, Page(s) e14963

Abstract: Introduction: Fibrosis of renal tubules is the final common pathway in diabetic nephropathy and develops in the face of tubular injury and fibroblast activation. Aberrant connexin 43 (Cx43) hemichannel activity has been linked to this damage under ... ...

Abstract	Introduction: Fibrosis of renal tubules is the final common pathway in diabetic nephropathy and develops in the face of tubular injury and fibroblast activation. Aberrant connexin 43 (Cx43) hemichannel activity has been linked to this damage under euglycaemic conditions, however, its role in glycaemic injury is unknown. This study investigated the effect of a Cx43 blocker (Tonabersat) on hemichannel activity and cell-cell interactions within and between tubular epithelial cells and fibroblasts in an in vitro model of diabetic nephropathy. Methods: Human kidney (HK2) proximal tubule epithelial cells and medullary fibroblasts (TK173) were treated in low (5 mM) or high (25 mM) glucose ± transforming growth factor beta-1 (TGFβ1) ± Tonabersat in high glucose. Carboxyfluorescein dye uptake and ATPlite luminescence assessed changes in hemichannel-mediated ATP release, while immunoblotting determined protein expression. Co-incubation with the ATP-diphosphohydrolase apyrase or a P2X7R inhibitor (A438079) assessed ATP-P2X7R signalling. Indirect co-culture with conditioned media from the alternate cell type evaluated paracrine-mediated heterotypic interactions. Results: Tonabersat partially negated glucose/TGFβ1-induced increases in Cx43 hemichannel-mediated ATP release and downstream changes in adherens junction and extracellular matrix (ECM) protein expression in HK2 and TK173 cells. Apyrase and A438079 highlighted the role for ATP-P2X7R in driving changes in protein expression in TK173 fibroblasts. Indirect co-culture studies suggest that epithelial cell secretome increases Tonabersat-sensitive hemichannel-mediated dye uptake in fibroblasts and downstream protein expression. Conclusion: Tonabersat-sensitive hemichannel-mediated ATP release enhances TGFβ1-driven heterotypic cell-cell interaction and favours myofibroblast activation. The data supports the potential benefit of Cx43 inhibition in reducing tubulointerstitial fibrosis in late-stage diabetic nephropathy.
MeSH term(s)	Humans ; Adenosine Triphosphate/metabolism ; Adenosine Triphosphate/pharmacology ; Apyrase/metabolism ; Apyrase/pharmacology ; Communication ; Connexin 43/metabolism ; Diabetes Mellitus/metabolism ; Diabetic Nephropathies/metabolism ; Epithelial Cells/metabolism ; Fibroblasts/metabolism ; Fibrosis ; Glucose/pharmacology
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Apyrase (EC 3.6.1.5) ; Connexin 43 ; Glucose (IY9XDZ35W2) ; tonabersat (2XD9773ZMN) ; GJA1 protein, human
Language	English
Publishing date	2022-10-25
Publishing country	England
Document type	Journal Article
ZDB-ID	605769-x
ISSN	1464-5491 ; 0742-3071 ; 1466-5468
ISSN (online)	1464-5491
ISSN	0742-3071 ; 1466-5468
DOI	10.1111/dme.14963
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 1954: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Connexin 43: A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes.

Cliff, Chelsy L / Williams, Bethany M / Chadjichristos, Christos E / Mouritzen, Ulrik / Squires, Paul E / Hills, Claire E

International journal of molecular sciences

2022 Volume 23, Issue 2

Abstract: Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease ...

Abstract	Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release 'danger signals' including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.
MeSH term(s)	Animals ; Connexin 43/metabolism ; Diabetes Complications/therapy ; Eye/pathology ; Humans ; Inflammation/metabolism ; Inflammation/therapy ; Kidney/pathology ; Microvessels/pathology
Chemical Substances	Connexin 43
Language	English
Publishing date	2022-01-06
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23020600
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Quantification of bush-cricket acoustic trachea mechanics using Atomic Force Microscopy nanoindentation.

Siamantouras, Eleftherios / Woodrow, Charlie / Celiker, Emine / Cullen, Darron A / Hills, Claire E / Squires, Paul E / Montealegre-Z, Fernando

Acta biomaterialia

2022 Volume 153, Page(s) 399–410

Abstract: Derived from the respiratory tracheae, bush-crickets' acoustic tracheae (or ear canals) are hollow tubes evolved to transmit sounds from the external environment to the interior ear. Due to the location of the ears in the forelegs, the acoustic trachea ... ...

Abstract	Derived from the respiratory tracheae, bush-crickets' acoustic tracheae (or ear canals) are hollow tubes evolved to transmit sounds from the external environment to the interior ear. Due to the location of the ears in the forelegs, the acoustic trachea serves as a structural element that can withstand large stresses during locomotion. In this study, we report a new Atomic Force Microscopy Force Spectroscopy (AFM-FS) approach to quantify the mechanics of taenidia in the bush-cricket Mecopoda elongata. Mechanical properties were examined over the longitudinal axis of hydrated taenidia, by indenting single fibres using precision hyperbolic tips. Analysis of the force-displacement (F-d) extension curves at low strains using the Hertzian contact model showed an Elastic modulus distribution between 13.9 MPa to 26.5 GPa, with a mean of 5.2 ± 7 GPa and median 1.03 GPa. Although chitin is the primary component of stiffness, variation of elasticity in the nanoscale suggests that resilin significantly affects the mechanical properties of single taenidia fibres (38% of total data). For indentations up to 400 nm, an intricate chitin-resilin response was observed, suggesting structural optimization between compliance and rigidity. Finite-element analysis on composite materials demonstrated that the Elastic modulus is sensitive to the percentage of resilin and chitin content, their location and structural configuration. Based on our results, we propose that the distinct moduli of taenidia fibres indicate sophisticated evolution with elasticity playing a key role in optimization. STATEMENT OF SIGNIFICANCE: In crickets and bush-crickets, the foreleg tracheae have evolved into acoustic canals, which transport sound to the ears located on the tibia of each leg. Tracheae are held open by spiral cuticular micro-fibres called taenidia, which are the primary elements of mechanical reinforcement. We developed an AFM-based method to indent individual taenidia at the nanometre level, to quantify local mechanical properties of the interior acoustic canal of the bush-cricket Mecopoda elongata, a model species in hearing research. Taenidia fibres were immobilized on a hard substrate and the indenter directly approached the epicuticle surface. This is the first characterization of the nano-structure of unfixed tracheal taenidia, and should pave the way for further in vivo mechanical investigations of auditory structures.
MeSH term(s)	Microscopy, Atomic Force/methods ; Trachea/physiology ; Elastic Modulus ; Elasticity ; Acoustics ; Chitin
Chemical Substances	Chitin (1398-61-4)
Language	English
Publishing date	2022-08-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2173841-5
ISSN	1878-7568 ; 1742-7061
ISSN (online)	1878-7568
ISSN	1742-7061
DOI	10.1016/j.actbio.2022.08.056
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Connexin-43 hemichannels orchestrate NOD-like receptor protein-3 (NLRP3) inflammasome activation and sterile inflammation in tubular injury.

Roger, Elena / Chadjichristos, Christos E / Kavvadas, Panagiotis / Price, Gareth W / Cliff, Chelsy L / Hadjadj, Safia / Renciot, Jessy / Squires, Paul E / Hills, Claire E

Cell communication and signaling : CCS

2023 Volume 21, Issue 1, Page(s) 263

Abstract: Background: Without a viable cure, chronic kidney disease is a global health concern. Inflammatory damage in and around the renal tubules dictates disease severity and is contributed to by multiple cell types. Activated in response to danger associated ... ...

Abstract	Background: Without a viable cure, chronic kidney disease is a global health concern. Inflammatory damage in and around the renal tubules dictates disease severity and is contributed to by multiple cell types. Activated in response to danger associated molecular patterns (DAMPs) including ATP, the NOD-like receptor protein-3 (NLRP3) inflammasome is integral to this inflammation. In vivo, we have previously observed that increased expression of Connexin 43 (Cx43) is linked to inflammation in chronic kidney disease (CKD) whilst in vitro studies in human proximal tubule cells highlight a role for aberrant Cx43 hemichannel mediated ATP release in tubule injury. A role for Cx43 hemichannels in priming and activation of the NLRP3 inflammasome in tubule epithelial cells remains to be determined. Methods: Using the Nephroseq database, analysis of unpublished transcriptomic data, examined gene expression and correlation in human CKD. The unilateral ureteral obstruction (UUO) mouse model was combined with genetic (tubule-specific Cx43 knockout) and specific pharmacological blockade of Cx43 (Peptide5), to explore a role for Cx43-hemichannels in tubule damage. Human primary tubule epithelial cells were used as an in vitro model of CKD. Results: Increased Cx43 and NLRP3 expression correlates with declining glomerular filtration rate and increased proteinuria in biopsies isolated from patients with CKD. Connexin 43-tubule deletion prior to UUO protected against tubular injury, increased expression of proinflammatory molecules, and significantly reduced NLRP3 expression and downstream signalling mediators. Accompanied by a reduction in F4/80 macrophages and fibroblast specific protein (FSP1 Conclusion: Aberrant Cx43-hemichannel activity in kidney tubule cells contributes to tubule inflammation via activation of the NLRP3 inflammasome and downstream paracrine mediated cell signalling. Use of hemichannel blockers in targeting Cx43-hemichannels is an attractive future therapeutic target to slow or prevent disease progression in CKD. Video Abstract.
MeSH term(s)	Animals ; Humans ; Mice ; Adenosine Triphosphate/metabolism ; Connexin 43/metabolism ; Inflammasomes/metabolism ; Inflammation/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism ; Renal Insufficiency, Chronic
Chemical Substances	Adenosine Triphosphate (8L70Q75FXE) ; Connexin 43 ; Inflammasomes ; NLR Family, Pyrin Domain-Containing 3 Protein ; GJA1 protein, human ; NLRP3 protein, human
Language	English
Publishing date	2023-09-28
Publishing country	England
Document type	Video-Audio Media ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2126315-2
ISSN	1478-811X ; 1478-811X
ISSN (online)	1478-811X
ISSN	1478-811X
DOI	10.1186/s12964-023-01245-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Examining Cell-Cell Interactions in the Kidney Using AFM Single-Cell Force Spectroscopy.

Siamantouras, Eleftherios / Hills, Claire E / Liu, Kuo-Kang / Squires, Paul E

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2067, Page(s) 189–201

Abstract: The ability of individual cells to synchronize activity is a basic feature of efficient and appropriate tissue function. Central to this is the physicochemical binding between cells through multiprotein complexes that functionally mediate adhesion. ... ...

Abstract	The ability of individual cells to synchronize activity is a basic feature of efficient and appropriate tissue function. Central to this is the physicochemical binding between cells through multiprotein complexes that functionally mediate adhesion. Importantly, the direct connection of physical properties and intercellular signaling is of great importance to certain pathologies including diabetes. Atomic force microscopy (AFM) single-cell force spectroscopy (SCFS) is a high-resolution technique that provides a statistically reliable measurement of the minute forces involved in cell tethering and membrane dynamics. Detection of altered nanoscale forces underlying the loss of adhesion in early tubular injury is pivotal for the development of novel therapeutic strategies for diabetic nephropathy. Here we describe the step-by-step use of an integrated AFM-SCFS system designed to measure functional force-displacement in separating renal tubular epithelial cells. Parameters such as unbinding forces, detachment energy, and distance to complete separation can be obtained from force-displacement (F-d) curves and are critical in assessing how physical changes of cellular adhesion contribute to cell contact, coupling, and communication in the diabetic kidney.
MeSH term(s)	Cell Adhesion/physiology ; Cell Communication/physiology ; Cell Line ; Diabetic Nephropathies/pathology ; Epithelial Cells/pathology ; Epithelial Cells/ultrastructure ; Humans ; Kidney Tubules/cytology ; Kidney Tubules/pathology ; Microscopy, Atomic Force/instrumentation ; Microscopy, Atomic Force/methods ; Single-Cell Analysis/instrumentation ; Single-Cell Analysis/methods ; Spectrum Analysis/instrumentation ; Spectrum Analysis/methods
Language	English
Publishing date	2019-12-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-4939-9841-8_14
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Connexin 43

Chelsy L. Cliff / Bethany M. Williams / Christos E. Chadjichristos / Ulrik Mouritzen / Paul E. Squires / Claire E. Hills

International Journal of Molecular Sciences, Vol 23, Iss 600, p

A Target for the Treatment of Inflammation in Secondary Complications of the Kidney and Eye in Diabetes

2022 Volume 600

Abstract	Of increasing prevalence, diabetes is characterised by elevated blood glucose and chronic inflammation that precedes the onset of multiple secondary complications, including those of the kidney and the eye. As the leading cause of end stage renal disease and blindness in the working population, more than ever is there a demand to develop clinical interventions which can both delay and prevent disease progression. Connexins are membrane bound proteins that can form pores (hemichannels) in the cell membrane. Gated by cellular stress and injury, they open under pathophysiological conditions and in doing so release ‘danger signals’ including adenosine triphosphate into the extracellular environment. Linked to sterile inflammation via activation of the nod-like receptor protein 3 inflammasome, targeting aberrant hemichannel activity and the release of these danger signals has met with favourable outcomes in multiple models of disease, including secondary complications of diabetes. In this review, we provide a comprehensive update on those studies which document a role for aberrant connexin hemichannel activity in the pathogenesis of both diabetic eye and kidney disease, ahead of evaluating the efficacy of blocking connexin-43 specific hemichannels in these target tissues on tissue health and function.
Keywords	diabetes ; complications ; diabetic nephropathy ; diabetic retinopathy ; connexin 43 ; hemichannels ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

Full text online

Full text

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Carboxyfluorescein Dye Uptake to Measure Connexin-mediated Hemichannel Activity in Cultured Cells.

Potter, Joe A / Price, Gareth W / Cliff, Chelsy L / Williams, Bethany M / Hills, Claire E / Squires, Paul E

Bio-protocol

2021 Volume 11, Issue 3, Page(s) e3901

Abstract: ... conditions, e.g. control versus disease. Other techniques, such as biotinylation and electrophysiology ...

Abstract	Connexins are membrane bound proteins that facilitate direct and local paracrine mediated cell-to-cell communication through their ability to oligomerise into hexameric hemichannels. When neighbouring channels align, they form gap-junctions that provide a direct route for information transfer between cells. In contrast to intact gap junctions, which typically open under physiological conditions, undocked hemichannels have a low open probability and mainly open in response to injury. Hemichannels permit the release of small molecules and ions (approximately 1kDa) into the local intercellular environment, and excessive expression/activity has been linked to a number of disease conditions. Carboxyfluorescein dye uptake measures functional expression of hemichannels, where increased hemichannel activity/function reflects increased loading. The technique relies on the uptake of a membrane-impermeable fluorescent tracer through open hemichannels, and can be used to compare channel activity between cell monolayers cultured under different conditions, e.g. control versus disease. Other techniques, such as biotinylation and electrophysiology can measure cell surface expression and hemichannel open probability respectively, however, carboxyfluorescein uptake provides a simple, rapid and cost-effective method to determine hemichannel activity
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	2833269-6
ISSN	2331-8325 ; 2331-8325
ISSN (online)	2331-8325
ISSN	2331-8325
DOI	10.21769/BioProtoc.3901
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Collagen I Modifies Connexin-43 Hemichannel Activity via Integrin α2β1 Binding in TGFβ1-Evoked Renal Tubular Epithelial Cells.

Potter, Joe A / Price, Gareth W / Cliff, Chelsy L / Green, Colin R / Squires, Paul E / Hills, Claire E

International journal of molecular sciences

2021 Volume 22, Issue 7

Abstract: Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to ... ...

Abstract	Chronic Kidney Disease (CKD) is associated with sustained inflammation and progressive fibrosis, changes that have been linked to altered connexin hemichannel-mediated release of adenosine triphosphate (ATP). Kidney fibrosis develops in response to increased deposition of extracellular matrix (ECM), and up-regulation of collagen I is an early marker of renal disease. With ECM remodeling known to promote a loss of epithelial stability, in the current study we used a clonal human kidney (HK2) model of proximal tubular epithelial cells to determine if collagen I modulates changes in cell function, via connexin-43 (Cx43) hemichannel ATP release. HK2 cells were cultured on collagen I and treated with the beta 1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± the Cx43 mimetic Peptide 5 and/or an anti-integrin α2β1 neutralizing antibody. Phase microscopy and immunocytochemistry observed changes in cell morphology and cytoskeletal reorganization, whilst immunoblotting and ELISA identified changes in protein expression and secretion. Carboxyfluorescein dye uptake and biosensing measured hemichannel activity and ATP release. A Cytoselect extracellular matrix adhesion assay assessed changes in cell-substrate interactions. Collagen I and TGFβ1 synergistically evoked increased hemichannel activity and ATP release. This was paralleled by changes to markers of tubular injury, partly mediated by integrin α2β1/integrin-like kinase signaling. The co-incubation of the hemichannel blocker Peptide 5, reduced collagen I/TGFβ1 induced alterations and inhibited a positive feedforward loop between Cx43/ATP release/collagen I. This study highlights a role for collagen I in regulating connexin-mediated hemichannel activity through integrin α2β1 signaling, ahead of establishing Peptide 5 as a potential intervention.
MeSH term(s)	Adenosine Triphosphate/metabolism ; Calcium/metabolism ; Cell Adhesion ; Cell Line ; Cells, Cultured ; Collagen Type I/metabolism ; Collagen Type I/physiology ; Connexin 43/metabolism ; Connexin 43/physiology ; Connexins/metabolism ; Cytokines ; Epithelial Cells/metabolism ; Humans ; Integrin alpha2beta1/metabolism ; Integrin alpha2beta1/physiology ; Kidney Tubules, Proximal/metabolism ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology ; Signal Transduction ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Collagen Type I ; Connexin 43 ; Connexins ; Cytokines ; Integrin alpha2beta1 ; Transforming Growth Factor beta1 ; Adenosine Triphosphate (8L70Q75FXE) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2021-03-31
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22073644
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Danegaptide Prevents TGFβ1-Induced Damage in Human Proximal Tubule Epithelial Cells of the Kidney.

Squires, Paul E / Price, Gareth W / Mouritzen, Ulrik / Potter, Joe A / Williams, Bethany M / Hills, Claire E

International journal of molecular sciences

2021 Volume 22, Issue 6

Abstract: Chronic kidney disease (CKD) is a global health problem associated with a number of comorbidities. Recent evidence implicates increased hemichannel-mediated release of adenosine triphosphate (ATP) in the progression of tubulointerstitial fibrosis, the ... ...

Abstract	Chronic kidney disease (CKD) is a global health problem associated with a number of comorbidities. Recent evidence implicates increased hemichannel-mediated release of adenosine triphosphate (ATP) in the progression of tubulointerstitial fibrosis, the main underlying pathology of CKD. Here, we evaluate the effect of danegaptide on blocking hemichannel-mediated changes in the expression and function of proteins associated with disease progression in tubular epithelial kidney cells. Primary human proximal tubule epithelial cells (hPTECs) were treated with the beta1 isoform of the pro-fibrotic cytokine transforming growth factor (TGFβ1) ± danegaptide. qRT-PCR and immunoblotting confirmed mRNA and protein expression, whilst a cytokine antibody array assessed the expression/secretion of proinflammatory and profibrotic cytokines. Carboxyfluorescein dye uptake and ATP biosensing measured hemichannel activity and ATP release, whilst transepithelial electrical resistance was used to assess paracellular permeability. Danegaptide negated carboxyfluorescein dye uptake and ATP release and protected against protein changes associated with tubular injury. Blocking Cx43-mediated ATP release was paralleled by partial restoration of the expression of cell cycle inhibitors, adherens and tight junction proteins and decreased paracellular permeability. Furthermore, danegaptide inhibited TGFβ1-induced changes in the expression and secretion of key adipokines, cytokines, chemokines, growth factors and interleukins. The data suggest that as a gap junction modulator and hemichannel blocker, danegaptide has potential in the future treatment of CKD.
MeSH term(s)	Cell Line ; Dipeptides/pharmacology ; Epithelial Cells/metabolism ; Epithelial Cells/pathology ; Humans ; Kidney Tubules, Proximal/injuries ; Kidney Tubules, Proximal/metabolism ; Kidney Tubules, Proximal/pathology ; Renal Insufficiency, Chronic/drug therapy ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/pathology ; Transforming Growth Factor beta1/metabolism
Chemical Substances	Dipeptides ; TGFB1 protein, human ; Transforming Growth Factor beta1 ; danegaptide (PA0Y7735AT)
Language	English
Publishing date	2021-03-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22062809
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

To top

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Inter-library loan at ZB MED

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito