Vascular Endothelial Cadherin Modulates Renal Interstitial Fibrosis

Overview

Journal Nephron Exp Nephrol

Publisher Karger

Specialties Biology
Nephrology

Date 2011 Dec 1

PMID 22126970

Citations 11

Authors

Ikuyo Yamaguchi

Bie Nga Tchao

Megan L Burger

Muneharu Yamada

Toshitake Hyodo

Costanza Giampietro

Allison A Eddy

Affiliations

Soon will be listed here.

Abstract

Background/aims: Renal interstitial fibrosis is a final common pathway of all chronic, progressive kidney diseases. Peritubular capillary rarefaction is strongly correlated with fibrosis. The adherens junction protein vascular endothelial cadherin (VE-cadherin) is thought to play a critical role in vascular integrity. We hypothesized that VE-cadherin modulates the renal microcirculation during fibrogenesis and ultimately affects renal fibrosis.

Methods: Unilateral ureteral obstruction (UUO) was used as a renal fibrosis model in VE-cadherin heterozygote (VE+/-) and wild-type (WT) mice, and the kidneys were harvested at days 3, 7, and 14. Peritubular capillary changes and fibrogenesis were investigated.

Results: VE+/- mice had lower levels of VE-cadherin protein than WT mice at 3 and 7, but not 14 days after UUO. Vascular permeability was significantly greater in VE+/- mice 7 days after UUO, while peritubular capillary density was not significantly different in VE+/- and WT mice. Interstitial myofibroblast numbers and collagen I and III mRNA levels were significantly higher in VE+/- mice, consistent with a stronger early fibrogenic response. Expression of the pericyte marker neuron-glial antigen 2 was upregulated after UUO, but was not greater in VE+/- mice compared to the WT mice.

Conclusion: Our data suggest that VE-cadherin controls vascular permeability and limits fibrogenesis after UUO.

Citing Articles

Mechanism of Chaihuang-Yishen formula to attenuate renal fibrosis in the treatment of chronic kidney disease: Insights from network pharmacology and experimental validation.

Miao J, Wei C, Wang H, Li Y, Yu X, Yang X Heliyon. 2024; 10(16):e35728.

PMID: 39220918 PMC: 11365344. DOI: 10.1016/j.heliyon.2024.e35728.

An update on renal fibrosis: from mechanisms to therapeutic strategies with a focus on extracellular vesicles.

Wang C, Li S, Zhong X, Liu B, Lv L Kidney Res Clin Pract. 2023; 42(2):174-187.

PMID: 37037480 PMC: 10085720. DOI: 10.23876/j.krcp.22.159.

Pirfenidone exacerbates Th2-driven vasculopathy in a mouse model of systemic sclerosis-associated interstitial lung disease.

Birnhuber A, Jandl K, Biasin V, Fliesser E, Valzano F, Marsh L Eur Respir J. 2022; 60(4).

PMID: 35332068 PMC: 9582508. DOI: 10.1183/13993003.02347-2021.

Depleted HDAC3 attenuates hyperuricemia-induced renal interstitial fibrosis via miR-19b-3p/SF3B3 axis.

Hu L, Yang K, Mai X, Wei J, Ma C Cell Cycle. 2022; 21(5):450-461.

PMID: 35025700 PMC: 8942505. DOI: 10.1080/15384101.2021.1989899.

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy.

Zhang A, Fang H, Chen J, He L, Chen Y Front Physiol. 2020; 11:1064.

PMID: 32982792 PMC: 7488177. DOI: 10.3389/fphys.2020.01064.

References

Dejana E . Endothelial cell-cell junctions: happy together. Nat Rev Mol Cell Biol. 2004; 5(4):261-70. DOI: 10.1038/nrm1357. View

Hallan S, Coresh J, Astor B, Asberg A, Powe N, Romundstad S . International comparison of the relationship of chronic kidney disease prevalence and ESRD risk. J Am Soc Nephrol. 2006; 17(8):2275-84. DOI: 10.1681/ASN.2005121273. View

Zhang B, Liang X, Shi W, Ye Z, He C, Hu X . Role of impaired peritubular capillary and hypoxia in progressive interstitial fibrosis after 56 subtotal nephrectomy of rats. Nephrology (Carlton). 2005; 10(4):351-7. DOI: 10.1111/j.1440-1797.2005.00412.x. View

Lelievre E, Mattot V, Huber P, Vandenbunder B, Soncin F . ETS1 lowers capillary endothelial cell density at confluence and induces the expression of VE-cadherin. Oncogene. 2000; 19(20):2438-46. DOI: 10.1038/sj.onc.1203563. View

Schumacher J, Puchakayala M, Binkowski K, EICHLER W, Dendorfer A, Klotz K . Effects of candesartan and enalaprilat on the organ-specific microvascular permeability during haemorrhagic shock in rats. Br J Anaesth. 2006; 96(4):437-43. DOI: 10.1093/bja/ael030. View

Zhang G, Kim H, Cai X, Lopez-Guisa J, Alpers C, Liu Y . Urokinase receptor deficiency accelerates renal fibrosis in obstructive nephropathy. J Am Soc Nephrol. 2003; 14(5):1254-71. DOI: 10.1097/01.asn.0000064292.37793.fb. View

Roussoulieres A, McGregor B, Chalabreysse L, Cerutti C, Garnier J, Boissonnat P . Expression of VE-Cadherin in Peritubular Endothelial Cells during Acute Rejection after Human Renal Transplantation. J Biomed Biotechnol. 2007; 2007(6):41705. PMC: 1940055. DOI: 10.1155/2007/41705. View

Matsumoto M, Tanaka T, Yamamoto T, Noiri E, Miyata T, Inagi R . Hypoperfusion of peritubular capillaries induces chronic hypoxia before progression of tubulointerstitial injury in a progressive model of rat glomerulonephritis. J Am Soc Nephrol. 2004; 15(6):1574-81. DOI: 10.1097/01.asn.0000128047.13396.48. View

von Tell D, Armulik A, Betsholtz C . Pericytes and vascular stability. Exp Cell Res. 2005; 312(5):623-9. DOI: 10.1016/j.yexcr.2005.10.019. View

10.

Rogers D, Boschetto P, Barnes P . Plasma exudation. Correlation between Evans blue dye and radiolabeled albumin in guinea pig airways in vivo. J Pharmacol Methods. 1989; 21(4):309-15. DOI: 10.1016/0160-5402(89)90068-5. View

11.

Kang D, Joly A, Oh S, Hugo C, Kerjaschki D, Gordon K . Impaired angiogenesis in the remnant kidney model: I. Potential role of vascular endothelial growth factor and thrombospondin-1. J Am Soc Nephrol. 2001; 12(7):1434-1447. DOI: 10.1681/ASN.V1271434. View

12.

Birdsey G, Dryden N, Amsellem V, Gebhardt F, Sahnan K, Haskard D . Transcription factor Erg regulates angiogenesis and endothelial apoptosis through VE-cadherin. Blood. 2008; 111(7):3498-506. PMC: 2275018. DOI: 10.1182/blood-2007-08-105346. View

13.

Horbelt M, Lee S, Mang H, Knipe N, Sado Y, Kribben A . Acute and chronic microvascular alterations in a mouse model of ischemic acute kidney injury. Am J Physiol Renal Physiol. 2007; 293(3):F688-95. DOI: 10.1152/ajprenal.00452.2006. View

14.

Boor P, Ostendorf T, Floege J . Renal fibrosis: novel insights into mechanisms and therapeutic targets. Nat Rev Nephrol. 2010; 6(11):643-56. DOI: 10.1038/nrneph.2010.120. View

15.

Yamaguchi I, Lopez-Guisa J, Cai X, Collins S, Okamura D, Eddy A . Endogenous urokinase lacks antifibrotic activity during progressive renal injury. Am J Physiol Renal Physiol. 2007; 293(1):F12-9. DOI: 10.1152/ajprenal.00380.2006. View

16.

Ishii Y, Sawada T, Kubota K, Fuchinoue S, Teraoka S, Shimizu A . Injury and progressive loss of peritubular capillaries in the development of chronic allograft nephropathy. Kidney Int. 2004; 67(1):321-32. DOI: 10.1111/j.1523-1755.2005.00085.x. View

17.

Gerber H, Hillan K, Ryan A, Kowalski J, Keller G, RANGELL L . VEGF is required for growth and survival in neonatal mice. Development. 1999; 126(6):1149-59. DOI: 10.1242/dev.126.6.1149. View

18.

Dejana E, Bazzoni G, Lampugnani M . Vascular endothelial (VE)-cadherin: only an intercellular glue?. Exp Cell Res. 1999; 252(1):13-9. DOI: 10.1006/excr.1999.4601. View

19.

Wallez Y, Vilgrain I, Huber P . Angiogenesis: the VE-cadherin switch. Trends Cardiovasc Med. 2006; 16(2):55-9. DOI: 10.1016/j.tcm.2005.11.008. View

20.

Kang D, Anderson S, Kim Y, Mazzalli M, Suga S, Jefferson J . Impaired angiogenesis in the aging kidney: vascular endothelial growth factor and thrombospondin-1 in renal disease. Am J Kidney Dis. 2001; 37(3):601-11. DOI: 10.1053/ajkd.2001.22087. View