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Article ; Online: Kidney Disease Associated With Mono-allelic

Groen In 't Woud, Sander / Rood, Ilse M / Steenbergen, Eric / Willemsen, Brigith / Dijkman, Henry B / van Geel, Michel / Schoots, Jeroen / Wetzels, Jack F M / Lugtenberg, Dorien / Deegens, Jeroen K J / Bongers, Ernie M H F

Kidney medicine

2023 Volume 5, Issue 4, Page(s) 100607

Abstract: Rationale & objective: Mono-allelic variants in : Study design: Case series.: Setting & participants: We evaluated clinical and pathologic characteristics of 17 Dutch index patients with mono-allelic variants in : Results: Eight different mono- ... ...

Abstract	Rationale & objective: Mono-allelic variants in Study design: Case series. Setting & participants: We evaluated clinical and pathologic characteristics of 17 Dutch index patients with mono-allelic variants in Results: Eight different mono-allelic Limitations: Retrospective design, ascertainment bias toward severe kidney phenotypes, and familial hematuria. Conclusions: This study confirms the wide phenotypic spectrum associated with mono-allelic
Language	English
Publishing date	2023-02-01
Publishing country	United States
Document type	Journal Article
ISSN	2590-0595
ISSN (online)	2590-0595
DOI	10.1016/j.xkme.2023.100607
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Article: Motile Cilia on Kidney Proximal Tubular Epithelial Cells Are Associated With Tubular Injury and Interstitial Fibrosis.

Eymael, Jennifer / Willemsen, Brigith / Xu, Joyce / Mooren, Fieke / Steenbergen, Eric / Wetzels, Jack F / Dijkman, Henry / Jansen, Jitske / Van der Vlag, Johan / Smeets, Bart

Frontiers in cell and developmental biology

2022 Volume 10, Page(s) 765887

Abstract: It is well established that mammalian kidney epithelial cells contain a single non-motile primary cilium (9 + 0 pattern). However, we noted the presence of multiple motile cilia with a central microtubular pair (9 + 2 pattern) in kidney biopsies of 11 ... ...

Abstract	It is well established that mammalian kidney epithelial cells contain a single non-motile primary cilium (9 + 0 pattern). However, we noted the presence of multiple motile cilia with a central microtubular pair (9 + 2 pattern) in kidney biopsies of 11 patients with various kidney diseases, using transmission electron microscopy. Immunofluorescence staining revealed the expression of the motile cilia-specific markers Radial Spoke Head Protein 4 homolog A, Forkhead-box-protein J1 and Regulatory factor X3. Multiciliated cells were exclusively observed in proximal tubuli and a relative frequent observation in human kidney tissue: in 16.7% of biopsies with tubular injury and atrophy (3 of 18 tissues), in 17.6% of biopsies from patients with membranous nephropathy (3 of 17 tissues) and in 10% of the human kidney tissues derived from the unaffected pole after tumour nephrectomy (3 of 30 tissues). However, these particular tissues showed marked tubular injury and fibrosis. Further analysis showed a significant relation between the presence of multiciliated cells and an increased expression of alpha-smooth-muscle-actin (
Language	English
Publishing date	2022-03-14
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2737824-X
ISSN	2296-634X
ISSN	2296-634X
DOI	10.3389/fcell.2022.765887
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Article ; Online: Parietal epithelial cells maintain the epithelial cell continuum forming Bowman's space in focal segmental glomerulosclerosis.

Disease models & mechanisms

2022 Volume 15, Issue 3

Abstract: In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated parietal epithelial cells (PECs) invading the glomerular ... ...

Abstract	In the glomerulus, Bowman's space is formed by a continuum of glomerular epithelial cells. In focal segmental glomerulosclerosis (FSGS), glomeruli show segmental scarring, a result of activated parietal epithelial cells (PECs) invading the glomerular tuft. The segmental scars interrupt the epithelial continuum. However, non-sclerotic segments seem to be preserved even in glomeruli with advanced lesions. We studied the histology of the segmental pattern in Munich Wistar Frömter rats, a model for secondary FSGS. Our results showed that matrix layers lined with PECs cover the sclerotic lesions. These PECs formed contacts with podocytes of the uninvolved tuft segments, restoring the epithelial continuum. Formed Bowman's spaces were still connected to the tubular system. In biopsies of patients with secondary FSGS, we also detected matrix layers formed by PECs, separating the uninvolved from the sclerotic glomerular segments. PECs have a major role in the formation of glomerulosclerosis; we show here that in FSGS they also restore the glomerular epithelial cell continuum that surrounds Bowman's space. This process may be beneficial and indispensable for glomerular filtration in the uninvolved segments of sclerotic glomeruli.
MeSH term(s)	Animals ; Bowman Capsule/pathology ; Epithelial Cells/pathology ; Female ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Kidney Glomerulus/pathology ; Male ; Rats ; Rats, Wistar
Language	English
Publishing date	2022-03-14
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2451104-3
ISSN	1754-8411 ; 1754-8403
ISSN (online)	1754-8411
ISSN	1754-8403
DOI	10.1242/dmm.046342
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Article ; Online: Human scattered tubular cells represent a heterogeneous population of glycolytic dedifferentiated proximal tubule cells.

Eymael, Jennifer / van den Broek, Martijn / Miesen, Laura / Monge, Valerie Villacorta / van den Berge, Bartholomeus T / Mooren, Fieke / Velez, Vicky Luna / Dijkstra, Jelmer / Hermsen, Meyke / Bándi, Péter / Vermeulen, Michiel / de Wildt, Saskia / Willemsen, Brigith / Florquin, Sandrine / Wetzels, Roy / Steenbergen, Eric / Kramann, Rafael / Moeller, Marcus / Schreuder, Michiel F /

Wetzels, Jack Fm / van der Vlag, Johan / Jansen, Jitske / Smeets, Bart

The Journal of pathology

2022 Volume 259, Issue 2, Page(s) 149–162

Abstract: Scattered tubular cells (STCs) are a phenotypically distinct cell population in the proximal tubule that increase in number after acute kidney injury. We aimed to characterize the human STC population. Three-dimensional human tissue analysis revealed ... ...

Abstract	Scattered tubular cells (STCs) are a phenotypically distinct cell population in the proximal tubule that increase in number after acute kidney injury. We aimed to characterize the human STC population. Three-dimensional human tissue analysis revealed that STCs are preferentially located within inner bends of the tubule and are barely present in young kidney tissue (<2 years), and their number increases with age. Increased STC numbers were associated with acute tubular injury (kidney injury molecule 1) and interstitial fibrosis (alpha smooth muscle actin). Isolated CD13
MeSH term(s)	Humans ; Kidney Tubules, Proximal/pathology ; Kidney/metabolism ; Acute Kidney Injury/metabolism ; Epithelial Cells ; Glycolysis
Language	English
Publishing date	2022-12-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3119-7
ISSN	1096-9896 ; 0022-3417
ISSN (online)	1096-9896
ISSN	0022-3417
DOI	10.1002/path.6029
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Article ; Online: Inhibition of mTOR delayed but could not prevent experimental collapsing focal segmental glomerulosclerosis.

Miesen, Laura / Eymael, Jennifer / Sharma, Shagun / Loeven, Markus A / Willemsen, Brigith / Bakker-van Bebber, Marinka / Mooren, Fieke / Meyer-Schwesinger, Catherine / Dijkman, Henry / Wetzels, Jack F M / Jansen, Jitske / van der Vlag, Johan / Smeets, Bart

Scientific reports

2020 Volume 10, Issue 1, Page(s) 8580

Abstract: Anti-Thy1.1 transgenic mice develop glomerular lesions that mimic collapsing focal segmental glomerulosclerosis (FSGS) in humans with collapse of the glomerular tuft and marked hyperplasia of the parietal epithelial cells (PECs). Immunostaining of ... ...

Abstract	Anti-Thy1.1 transgenic mice develop glomerular lesions that mimic collapsing focal segmental glomerulosclerosis (FSGS) in humans with collapse of the glomerular tuft and marked hyperplasia of the parietal epithelial cells (PECs). Immunostaining of phosphor-S6 ribosomal protein (pS6RP) revealed high mTOR activity in PECs of the FSGS lesions of these mice. In this study we questioned whether the mTOR inhibitor rapamycin (sirolimus) could attenuate the development and progression of glomerulosclerotic lesions in the anti-Thy1.1 transgenic mice. We observed reduced mTOR signalling and proliferation in human parietal epithelial cells after rapamycin treatment. Experiments with anti-Thy1.1. mice showed that early treatment with sirolimus reduced the development of glomerular lesions and glomerular cell proliferation at day 4. Levels of albuminuria, podocyte injury and podocyte number were similar in the sirolimus and vehicle treated groups. The initial beneficial effects of sirolimus treatment were not observed at day 7. Late sirolimus treatment did not reduce albuminuria or the progression of glomerulosclerosis. Taken together, rapamycin attenuated PEC proliferation and the formation of early FSGS lesions in experimental FSGS and reduced human PEC proliferation in vitro. However, the initial inhibition of PEC proliferation did not translate into a decline of albuminuria nor in a sustained reduction in sclerotic lesions.
MeSH term(s)	Albuminuria/drug therapy ; Albuminuria/metabolism ; Albuminuria/pathology ; Animals ; Cell Proliferation ; Glomerulosclerosis, Focal Segmental/drug therapy ; Glomerulosclerosis, Focal Segmental/metabolism ; Glomerulosclerosis, Focal Segmental/pathology ; Humans ; Immunosuppressive Agents/pharmacology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Sclerosis/drug therapy ; Sclerosis/metabolism ; Sclerosis/pathology ; Signal Transduction ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; TOR Serine-Threonine Kinases/genetics ; TOR Serine-Threonine Kinases/metabolism ; Thy-1 Antigens/physiology
Chemical Substances	Immunosuppressive Agents ; Thy-1 Antigens ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; mTOR protein, mouse (EC 2.7.1.1) ; Sirolimus (W36ZG6FT64)
Language	English
Publishing date	2020-05-22
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-020-65352-y
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Article ; Online: Distribution and Function of PACAP and Its Receptors in the Healthy and Nephrotic Kidney.

Eneman, Benedicte / van den Heuvel, Lambertus / Freson, Kathleen / Van Geet, Chris / Willemsen, Brigith / Dijkman, Henry / Levtchenko, Elena

Nephron

2016 Volume 132, Issue 4, Page(s) 301–311

Abstract: Background/aims: Plasma deficiency of pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome (NS). Previous studies have reported an important protective effect of PACAP on kidney ... ...

Abstract	Background/aims: Plasma deficiency of pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome (NS). Previous studies have reported an important protective effect of PACAP on kidney proximal tubules. The aim of this study was to explore the expression of PACAP and its receptors PAC1, VPAC1 and VPAC2 in the healthy and nephrotic kidney and to determine if PACAP has an effect on renal proximal tubular cells exposed to albumin. Methods: Expression of PACAP and its receptors was studied using kidney tissue from healthy and nephrotic children, and in 3 human renal cell lines (glomerular microvascular endothelial cells, podocytes and proximal tubular epithelial HK-2 cells). The functionality of the VPAC1 receptor was tested in HK-2 cells, measuring cyclic adenosine monophosphate levels after PACAP exposure. The influence of PACAP on cell viability and transforming growth factor-β1 (TGF-β1) expression was measured in HK-2 cells exposed to albumin, mimicking proteinuria related damage. Results: VPAC1 expression was detected in the tubular proximal epithelial cells and in the glomerular podocytes of renal tissue from healthy and nephrotic children. Increased staining for PACAP was found in the proximal tubules of renal sections from children with NS compared to healthy renal sections. Expression and functionality of VPAC1 were demonstrated in HK-2 cells. Finally, PACAP did not alter cell viability or TGF-β1 expression of HK-2 cells exposed to albumin. Conclusion: VPAC1 is the predominant receptor in the human kidney. The enhanced presence of PACAP in proximal tubular epithelial cells in nephrotic kidneys points to the reabsorption of filtered PACAP. On short term, PACAP has no in vitro effect on cell viability and TGF-β1 expression of proximal tubular epithelial cells exposed to high concentrations of albumin.
MeSH term(s)	Cell Line, Transformed ; Humans ; Kidney Diseases/metabolism ; Kidney Tubules, Proximal/cytology ; Kidney Tubules, Proximal/metabolism ; Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism
Chemical Substances	Pituitary Adenylate Cyclase-Activating Polypeptide ; Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide
Language	English
Publishing date	2016
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000445035
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Zs.A 169: Show issues

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Article ; Online: Cathepsin L is crucial for the development of early experimental diabetic nephropathy.

Garsen, Marjolein / Rops, Angelique L W M M / Dijkman, Henry / Willemsen, Brigith / van Kuppevelt, Toin H / Russel, Frans G / Rabelink, Ton J / Berden, Jo H M / Reinheckel, Thomas / van der Vlag, Johan

Kidney international

2016 Volume 90, Issue 5, Page(s) 1012–1022

Abstract: Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of ... ...

Abstract	Proteinuria is one of the first clinical signs of diabetic nephropathy and an independent predictor for the progression to renal failure. Cathepsin L, a lysosomal cysteine protease, can be involved in the development of proteinuria by degradation of proteins that are important for normal podocyte architecture, such as the CD2-associated protein, synaptopodin, and dynamin. Cathepsin L also activates heparanase, a heparan sulfate endoglycosidase previously shown to be crucial for the development of diabetic nephropathy. Here, we evaluated the exact mode of action of cathepsin L in the development of proteinuria in streptozotocin-induced diabetes. Cathepsin L-deficient mice, in contrast to their wild-type littermates, failed to develop albuminuria, mesangial matrix expansion, tubulointerstitial fibrosis, and renal macrophage influx and showed a normal renal function. In wild-type mice the early development of albuminuria correlated with the activation of heparanase and loss of heparan sulfate expression, whereas loss of synaptopodin expression and podocyte damage occurred at a later stage. Thus, cathepsin L is causally involved in the pathogenesis of experimental diabetic nephropathy. Most likely, cathepsin L-dependent heparanase activation is crucial for the development of albuminuria and renal damage.
MeSH term(s)	Adaptor Proteins, Signal Transducing/metabolism ; Animals ; Cathepsin L/metabolism ; Cytoskeletal Proteins/metabolism ; Diabetes Mellitus, Experimental/complications ; Diabetic Nephropathies/etiology ; Dynamins/metabolism ; Glucuronidase/metabolism ; Mice, Inbred C57BL ; Microfilament Proteins/metabolism
Chemical Substances	Adaptor Proteins, Signal Transducing ; CD2-associated protein ; Cytoskeletal Proteins ; Microfilament Proteins ; Synpo protein, mouse ; heparanase (EC 3.2.1.-) ; Glucuronidase (EC 3.2.1.31) ; Cathepsin L (EC 3.4.22.15) ; Dynamins (EC 3.6.5.5)
Language	English
Publishing date	2016-08-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1016/j.kint.2016.06.035
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Article ; Online: Endothelin-1 Induces Proteinuria by Heparanase-Mediated Disruption of the Glomerular Glycocalyx.

Garsen, Marjolein / Lenoir, Olivia / Rops, Angelique L W M M / Dijkman, Henry B / Willemsen, Brigith / van Kuppevelt, Toin H / Rabelink, Ton J / Berden, Jo H M / Tharaux, Pierre-Louis / van der Vlag, Johan

Journal of the American Society of Nephrology : JASN

2016 Volume 27, Issue 12, Page(s) 3545–3551

Abstract: Diabetic nephropathy (DN) is the leading cause of CKD in the Western world. Endothelin receptor antagonists have emerged as a novel treatment for DN, but the mechanisms underlying the protective effect remain unknown. We previously showed that both ... ...

Abstract	Diabetic nephropathy (DN) is the leading cause of CKD in the Western world. Endothelin receptor antagonists have emerged as a novel treatment for DN, but the mechanisms underlying the protective effect remain unknown. We previously showed that both heparanase and endothelin-1 are essential for the development of DN. Here, we further investigated the role of these proteins in DN, and demonstrated that endothelin-1 activates podocytes to release heparanase. Furthermore, conditioned podocyte culture medium increased glomerular transendothelial albumin passage in a heparanase-dependent manner. In mice, podocyte-specific knockout of the endothelin receptor prevented the diabetes-induced increase in glomerular heparanase expression, consequent reduction in heparan sulfate expression and endothelial glycocalyx thickness, and development of proteinuria observed in wild-type counterparts. Our data suggest that in diabetes, endothelin-1 signaling, as occurs in endothelial activation, induces heparanase expression in the podocyte, damage to the glycocalyx, proteinuria, and renal failure. Thus, prevention of these effects may constitute the mechanism of action of endothelin receptor blockers in DN.
MeSH term(s)	Animals ; Diabetic Nephropathies/etiology ; Endothelin-1/physiology ; Glucuronidase/physiology ; Glycocalyx/enzymology ; Kidney Glomerulus/enzymology ; Kidney Glomerulus/ultrastructure ; Male ; Mice ; Podocytes/enzymology ; Proteinuria/etiology
Chemical Substances	Endothelin-1 ; heparanase (EC 3.2.1.-) ; Glucuronidase (EC 3.2.1.31)
Language	English
Publishing date	2016-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2015091070
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Article ; Online: Autophagy activity is associated with membranous sodium iodide symporter expression and clinical response to radioiodine therapy in non-medullary thyroid cancer.

Plantinga, Theo S / Tesselaar, Marika H / Morreau, Hans / Corssmit, Eleonora P M / Willemsen, Brigith K / Kusters, Benno / van Engen-van Grunsven, A C H / Smit, Johannes W A / Netea-Maier, Romana T

Autophagy

2016 Volume 12, Issue 7, Page(s) 1195–1205

Abstract: Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are ... ...

Abstract	Although non-medullary thyroid cancer (NMTC) generally has a good prognosis, 30-40% of patients with distant metastases develop resistance to radioactive iodine (RAI) therapy due to tumor dedifferentiation. For these patients, treatment options are limited and prognosis is poor. In the present study, expression and activity of autophagy was assessed in large sets of normal, benign and malignant tissues and was correlated with pathology, SLC5A5/hNIS (solute carrier family 5 member 5) protein expression, and with clinical response to RAI ablation therapy in NMTC patients. Fluorescent immunostaining for the autophagy marker LC3 was performed on 100 benign and 80 malignant thyroid tissues. Semiquantitative scoring was generated for both diffuse LC3-I intensity and number of LC3-II-positive puncta and was correlated with SLC5A5 protein expression and clinical parameters. Degree of diffuse LC3-I intensity and number of LC3-II-positive puncta scoring were not discriminative for benign vs. malignant thyroid lesions. Interestingly, however, in NMTC patients significant associations were observed between diffuse LC3-I intensity and LC3-II-positive puncta scoring on the one hand and clinical response to RAI therapy on the other hand (odds ratio [OR] = 3.13, 95% confidence interval [CI] =1.91-5.12, P = 0.01; OR = 5.68, 95%CI = 3.02-10.05, P = 0.002, respectively). Mechanistically, the number of LC3-II-positive puncta correlated with membranous SLC5A5 expression (OR = 7.71, 95%CI = 4.15-11.75, P<0.001), number of RAI treatments required to reach remission (P = 0.014), cumulative RAI dose (P = 0.026) and with overall remission and recurrence rates (P = 0.031). In conclusion, autophagy activity strongly correlates with clinical response of NMTC patients to RAI therapy, potentially by its capacity to maintain tumor cell differentiation and to preserve functional iodide uptake.
MeSH term(s)	Autophagy/drug effects ; Carcinoma, Papillary/diagnosis ; Carcinoma, Papillary/drug therapy ; Humans ; Iodine Radioisotopes/therapeutic use ; Prognosis ; Symporters/metabolism ; Thyroid Cancer, Papillary ; Thyroid Neoplasms/diagnosis ; Thyroid Neoplasms/drug therapy
Chemical Substances	Iodine Radioisotopes ; Symporters ; sodium-iodide symporter (4XE5NDT4K1)
Language	English
Publishing date	2016-04-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	2454135-7
ISSN	1554-8635 ; 1554-8627
ISSN (online)	1554-8635
ISSN	1554-8627
DOI	10.1080/15548627.2016.1174802
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Article: Distribution and Function of PACAP and Its Receptors in the Healthy and Nephrotic Kidney

Eneman, Benedicte / van den Heuvel, Lambertus / Freson, Kathleen / Van Geet, Chris / Willemsen, Brigith / Dijkman, Henry / Levtchenko, Elena

Nephron

2016 Volume 132, Issue 4, Page(s) 301–311

Abstract: Background/Aims: Plasma deficiency of pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome (NS). Previous studies have reported an important protective effect of PACAP on kidney proximal ...

Institution	Pediatric Nephrology, Department of Development and Regeneration, University Hospitals of Leuven, and Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, University of Leuven, Leuven, Belgium Department of Pediatric Nephrology and Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
Abstract	Background/Aims: Plasma deficiency of pituitary adenylate cyclase-activating polypeptide (PACAP) was recently demonstrated in children with nephrotic syndrome (NS). Previous studies have reported an important protective effect of PACAP on kidney proximal tubules. The aim of this study was to explore the expression of PACAP and its receptors PAC1, VPAC1 and VPAC2 in the healthy and nephrotic kidney and to determine if PACAP has an effect on renal proximal tubular cells exposed to albumin. Methods: Expression of PACAP and its receptors was studied using kidney tissue from healthy and nephrotic children, and in 3 human renal cell lines (glomerular microvascular endothelial cells, podocytes and proximal tubular epithelial HK-2 cells). The functionality of the VPAC1 receptor was tested in HK-2 cells, measuring cyclic adenosine monophosphate levels after PACAP exposure. The influence of PACAP on cell viability and transforming growth factor-β1 (TGF-β1) expression was measured in HK-2 cells exposed to albumin, mimicking proteinuria related damage. Results: VPAC1 expression was detected in the tubular proximal epithelial cells and in the glomerular podocytes of renal tissue from healthy and nephrotic children. Increased staining for PACAP was found in the proximal tubules of renal sections from children with NS compared to healthy renal sections. Expression and functionality of VPAC1 were demonstrated in HK-2 cells. Finally, PACAP did not alter cell viability or TGF-β1 expression of HK-2 cells exposed to albumin. Conclusion: VPAC1 is the predominant receptor in the human kidney. The enhanced presence of PACAP in proximal tubular epithelial cells in nephrotic kidneys points to the reabsorption of filtered PACAP. On short term, PACAP has no in vitro effect on cell viability and TGF-β1 expression of proximal tubular epithelial cells exposed to high concentrations of albumin.
Keywords	VPAC1 ; Pituitary adenylate cyclase-activating polypeptide ; Proteinuria ; Proximal tubular epithelial cells
Language	English
Publishing date	2016-04-07
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Experimental Nephrology and Genetics: Original Paper
ZDB-ID	207121-6
ISSN	2235-3186 ; 1423-0186 ; 1660-8151 ; 0028-2766
ISSN (online)	2235-3186 ; 1423-0186
ISSN	1660-8151 ; 0028-2766
DOI	10.1159/000445035
Database	Karger publisher's database

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