Semaphorin3a Signaling, Podocyte Shape, and Glomerular Disease

Overview

Journal Pediatr Nephrol

Specialties Nephrology
Pediatrics

Date 2014 Jan 28

PMID 24464477

Citations 7

Authors

Alda Tufro

Affiliations

Soon will be listed here.

Abstract

Semaphorin3a (sema3a), a member of class 3 semaphorins, is a guidance protein that regulates angiogenesis, branching morphogenesis, axon growth, and cell migration, and has pleiotropic roles on organogenesis, immune response, and cancer. Sema3a is secreted by podocytes and is required for normal kidney patterning and glomerular filtration barrier development. We recently discovered that after completion of kidney development, Sema3a gain-of-function in podocytes leads to proteinuric glomerular disease in mice. Excess sema3a causes foot process effacement, glomerular basement lamination, and endothelial damage in vivo, and disrupts cell autonomously podocyte shape by down-regulating nephrin and inhibiting αvβ3 integrin. We identified a novel direct interaction between nephrin and plexinA1, the sema3a signaling receptor. Nephrin-plexinA1 interaction links the slit-diaphragm signaling complex to extracellular sema3a signals. Hence, sema3a functions as an extracellular negative regulator of the structure and function of the glomerular filtration barrier.

Citing Articles

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Role of Semaphorin 3A in Kidney Development and Diseases.

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Semaphorin3A-Inhibitor Ameliorates Doxorubicin-Induced Podocyte Injury.

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A Preliminary Study of the Effect of Semaphorin 3A and Acitretin on the Proliferation, Migration, and Apoptosis of HaCaT Cells.

Ding W, Cao Y, Xing F, Tao M, Fu H, Luo H Indian J Dermatol. 2019; 64(3):250.

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Gpr97 Exacerbates AKI by Mediating Sema3A Signaling.

Fang W, Wang Z, Li Q, Wang X, Zhang Y, Sun Y J Am Soc Nephrol. 2018; 29(5):1475-1489.

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References

Serini G, Valdembri D, Zanivan S, Morterra G, Burkhardt C, Caccavari F . Class 3 semaphorins control vascular morphogenesis by inhibiting integrin function. Nature. 2003; 424(6947):391-7. DOI: 10.1038/nature01784. View

Hinck L . The versatile roles of "axon guidance" cues in tissue morphogenesis. Dev Cell. 2004; 7(6):783-93. DOI: 10.1016/j.devcel.2004.11.002. View

Perala N, Sariola H, Immonen T . More than nervous: the emerging roles of plexins. Differentiation. 2011; 83(1):77-91. DOI: 10.1016/j.diff.2011.08.001. View

Veron D, Bertuccio C, Marlier A, Reidy K, Garcia A, Jimenez J . Podocyte vascular endothelial growth factor (Vegf₁₆₄) overexpression causes severe nodular glomerulosclerosis in a mouse model of type 1 diabetes. Diabetologia. 2011; 54(5):1227-41. PMC: 3397150. DOI: 10.1007/s00125-010-2034-z. View

Veron D, Villegas G, Aggarwal P, Bertuccio C, Jimenez J, Velazquez H . Acute podocyte vascular endothelial growth factor (VEGF-A) knockdown disrupts alphaVbeta3 integrin signaling in the glomerulus. PLoS One. 2012; 7(7):e40589. PMC: 3396653. DOI: 10.1371/journal.pone.0040589. View

Coultas L, Chawengsaksophak K, Rossant J . Endothelial cells and VEGF in vascular development. Nature. 2005; 438(7070):937-45. DOI: 10.1038/nature04479. View

Tufro A, Teichman J, Woda C, Villegas G . Semaphorin3a inhibits ureteric bud branching morphogenesis. Mech Dev. 2008; 125(5-6):558-68. PMC: 3992265. DOI: 10.1016/j.mod.2007.12.003. View

Kreidberg J, Donovan M, Goldstein S, Rennke H, Shepherd K, Jones R . Alpha 3 beta 1 integrin has a crucial role in kidney and lung organogenesis. Development. 1996; 122(11):3537-47. DOI: 10.1242/dev.122.11.3537. View

Villegas G, Tufro A . Ontogeny of semaphorins 3A and 3F and their receptors neuropilins 1 and 2 in the kidney. Mech Dev. 2003; 119 Suppl 1:S149-53. DOI: 10.1016/s0925-4773(03)00108-4. View

10.

Reidy K, Tufro A . Semaphorins in kidney development and disease: modulators of ureteric bud branching, vascular morphogenesis, and podocyte-endothelial crosstalk. Pediatr Nephrol. 2011; 26(9):1407-12. PMC: 3397149. DOI: 10.1007/s00467-011-1769-1. View

11.

Behar O, Golden J, Mashimo H, Schoen F, Fishman M . Semaphorin III is needed for normal patterning and growth of nerves, bones and heart. Nature. 1996; 383(6600):525-8. DOI: 10.1038/383525a0. View

12.

Yu C, Fornoni A, Weins A, Hakroush S, Maiguel D, Sageshima J . Abatacept in B7-1-positive proteinuric kidney disease. N Engl J Med. 2013; 369(25):2416-23. PMC: 3951406. DOI: 10.1056/NEJMoa1304572. View

13.

Wei C, El Hindi S, Li J, Fornoni A, Goes N, Sageshima J . Circulating urokinase receptor as a cause of focal segmental glomerulosclerosis. Nat Med. 2011; 17(8):952-60. PMC: 4089394. DOI: 10.1038/nm.2411. View

14.

Seiler M, Venkatachalam M, COTRAN R . Glomerular epithelium: structural alterations induced by polycations. Science. 1975; 189(4200):390-3. DOI: 10.1126/science.1145209. View

15.

Doi K, Noiri E, Nangaku M, Yahagi N, Jayakumar C, Ramesh G . Repulsive guidance cue semaphorin 3A in urine predicts the progression of acute kidney injury in adult patients from a mixed intensive care unit. Nephrol Dial Transplant. 2013; 29(1):73-80. PMC: 3888311. DOI: 10.1093/ndt/gft414. View

16.

Reidy K, Villegas G, Teichman J, Veron D, Shen W, Jimenez J . Semaphorin3a regulates endothelial cell number and podocyte differentiation during glomerular development. Development. 2009; 136(23):3979-89. PMC: 2778745. DOI: 10.1242/dev.037267. View

17.

Guan F, Villegas G, Teichman J, Mundel P, Tufro A . Autocrine class 3 semaphorin system regulates slit diaphragm proteins and podocyte survival. Kidney Int. 2006; 69(9):1564-9. DOI: 10.1038/sj.ki.5000313. View

18.

Tran T, Kolodkin A, Bharadwaj R . Semaphorin regulation of cellular morphology. Annu Rev Cell Dev Biol. 2007; 23:263-92. DOI: 10.1146/annurev.cellbio.22.010605.093554. View

19.

Kolodkin A, Levengood D, Rowe E, Tai Y, Giger R, Ginty D . Neuropilin is a semaphorin III receptor. Cell. 1997; 90(4):753-62. DOI: 10.1016/s0092-8674(00)80535-8. View

20.

Miao H, Soker S, FEINER L, Alonso J, Raper J, Klagsbrun M . Neuropilin-1 mediates collapsin-1/semaphorin III inhibition of endothelial cell motility: functional competition of collapsin-1 and vascular endothelial growth factor-165. J Cell Biol. 1999; 146(1):233-42. PMC: 2199727. DOI: 10.1083/jcb.146.1.233. View