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Open Access 01-12-2020 | Glomerulonephritis | Mini review

A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney

Authors: Ines Marek, Karl Friedrich Hilgers, Wolfgang Rascher, Joachim Woelfle, Andrea Hartner

Published in: Molecular and Cellular Pediatrics | Issue 1/2020

Abstract

Glomerulonephritis results in a dysregulation of glomerular cells and may end up in chronic alterations and subsequent loss of renal function. Therefore, understanding mechanisms, which contribute to maintain glomerular integrity, is a pivotal prerequisite for therapeutic interventions. The alpha-8 integrin chain seems to be an important player to maintain glomerular homeostasis by conferring mechanical stability and functional support for the renal capillary tuft.

Pan CG (1997) Glomerulonephritis in childhood. Curr Opin Pediatr 9:154–159. https://doi.org/10.1097/00008480-199704000-00007CrossRefPubMed

Veis JH, Yamashita W, Liu YJ, Ooi BS (1990) The biology of mesangial cells in glomerulonephritis. Proc Soc Exp Biol Med 195:160–167. https://doi.org/10.3181/00379727-195-43129aCrossRefPubMed

Kimmel M, Kuhlmann U (2015) Glomerulonephritis. In: Kuhlmann U, Böhler J, Luft FC, Alscher MD, Kunzendorf U (eds) Nephrologie, 6th edn. Georg Thieme Verlag, Stuttgart

Savill J, Smith J, Sarraf C, Ren Y, Abbott F, Rees A (1992) Glomerular mesangial cells and inflammatory macrophages ingest neutrophils undergoing apoptosis. Kidney Int 42:924–936. https://doi.org/10.1038/ki.1992.369CrossRefPubMed

Sterzel RB, Schulze-Lohoff E, Weber M, Goodman SL (1992) Interactions between glomerular mesangial cells, cytokines, and extracellular matrix. J Am Soc Nephrol 2:S126–S131PubMed

Hynes RO (2002) Integrins: bidirectional, allosteric signaling machines. Cell 110:673–687. https://doi.org/10.1016/s0092-8674(02)00971-6CrossRefPubMed

Hynes RO (2004) The emergence of integrins: a personal and historical perspective. Matrix Biol 23:333–340. https://doi.org/10.1016/j.matbio.2004.08.001CrossRefPubMedPubMedCentral

Streuli CH (2016) Integrins as architects of cell behavior. Mol Biol Cell 27:2885–2888. https://doi.org/10.1091/mbc.E15-06-0369CrossRefPubMedPubMedCentral

Sayedyahossein S, Dagnino L (2013) Integrins and small GTPases as modulators of phagocytosis. Int Rev Cell Mol Biol 302:321–354. https://doi.org/10.1016/B978-0-12-407699-0.00006-6CrossRefPubMed

10.

Humphries MJ (2002) Insights into integrin-ligand binding and activation from the first crystal structure. Arthritis Res 4(Suppl 3):S69–S78. https://doi.org/10.1186/ar563CrossRefPubMedPubMedCentral

11.

Hartner A, Dötsch J (2002) Lessons in congenital and acquired renal disease from alpha8 integrin mutant mice. Pediatr Nephrol 17:882–888. https://doi.org/10.1007/s00467-002-0950-yCrossRefPubMed

12.

Schedl A (2007) Renal abnormalities and their developmental origin. Nat Rev Genet 8:791–802. https://doi.org/10.1038/nrg2205CrossRefPubMed

13.

Müller U, Wang D, Denda S, Meneses JJ, Pedersen RA, Reichardt LF (1997) Integrin alpha8beta1 is critically important for epithelial-mesenchymal interactions during kidney morphogenesis. Cell 88:603–613. https://doi.org/10.1016/s0092-8674(00)81903-0CrossRefPubMedPubMedCentral

14.

Brandenberger R, Schmidt A, Linton J, Wang D, Backus C, Denda S, Müller U, Reichardt LF (2001) Identification and characterization of a novel extracellular matrix protein nephronectin that is associated with integrin alpha8beta1 in the embryonic kidney. J Cell Biol 154:447–458. https://doi.org/10.1083/jcb.200103069CrossRefPubMedPubMedCentral

15.

Linton JM, Martin GR, Reichardt LF (2007) The ECM protein nephronectin promotes kidney development via integrin alpha8beta1-mediated stimulation of Gdnf expression. Development 134:2501–2509. https://doi.org/10.1242/dev.005033CrossRefPubMedPubMedCentral

16.

Cullen-McEwen LA, Drago J, Bertram JF (2001) Nephron endowment in glial cell line-derived neurotrophic factor (GDNF) heterozygous mice. Kidney Int 60:31–36. https://doi.org/10.1046/j.1523-1755.2001.00767.xCrossRefPubMed

17.

Humbert C, Silbermann F, Morar B, Parisot M, Zarhrate M, Masson C, Tores F, Blanchet P, Perez MJ, Petrov Y, Khau Van Kien P, Roume J, Leroy B, Gribouval O, Kalaydjieva L, Heidet L, Salomon R, Antignac C, Benmerah A, Saunier S, Jeanpierre C (2014) Integrin alpha 8 recessive mutations are responsible for bilateral renal agenesis in humans. Am J Hum Genet 94:288–294. https://doi.org/10.1016/j.ajhg.2013.12.017CrossRefPubMedPubMedCentral

18.

Hartner A, Schöcklmann H, Pröls F, Müller U, Sterzel RB (1999) Alpha8 integrin in glomerular mesangial cells and in experimental glomerulonephritis. Kidney Int 56:1468–1480. https://doi.org/10.1046/j.1523-1755.1999.00662.xCrossRefPubMed

19.

Lu Y, Ye Y, Yang Q, Shi S (2017) Single-cell RNA-sequence analysis of mouse glomerular mesangial cells uncovers mesangial cell essential genes. Kidney Int 92:504–513. https://doi.org/10.1016/j.kint.2017.01.016CrossRefPubMed

20.

Bieritz B, Spessotto P, Colombatti A, Jahn A, Prols F, Hartner A (2003) Role of alpha8 integrin in mesangial cell adhesion, migration, and proliferation. Kidney Int 64:119–127. https://doi.org/10.1046/j.1523-1755.2003.00057.xCrossRefPubMed

21.

Hartner A, Cordasic N, Klanke B, Müller U, Sterzel RB, Hilgers KF (2002) The alpha8 integrin chain affords mechanical stability to the glomerular capillary tuft in hypertensive glomerular disease. Am J Pathol 160:861–867. https://doi.org/10.1016/s0002-9440(10)64909-7CrossRefPubMedPubMedCentral

22.

Scindia YM, Deshmukh US, Bagavant H (2010) Mesangial pathology in glomerular disease: targets for therapeutic intervention. Adv Drug Deliv Rev 62:1337–1343. https://doi.org/10.1016/j.addr.2010.08.011CrossRefPubMedPubMedCentral

23.

Baker AJ, Mooney A, Hughes J, Lombardi D, Johnson RJ, Savill J (1994) Mesangial cell apoptosis: the major mechanism for resolution of glomerular hypercellularity in experimental mesangial proliferative nephritis. J Clin Invest 94:2105–2116. https://doi.org/10.1172/jci117565CrossRefPubMedPubMedCentral

24.

Watson S, Cailhier JF, Hughes J, Savill J (2006) Apoptosis and glomerulonephritis. Curr Dir Autoimmun 9:188–204. https://doi.org/10.1159/000090782CrossRefPubMed

25.

Benoit YD, Lussier C, Ducharme PA, Sivret S, Schnapp LM, Basora N, Beaulieu JF (2009) Integrin alpha8beta1 regulates adhesion, migration and proliferation of human intestinal crypt cells via a predominant RhoA/ROCK-dependent mechanism. Biol Cell 101:695–708. https://doi.org/10.1042/bc20090060CrossRefPubMedPubMedCentral

26.

Farias E, Lu M, Li X, Schnapp LM (2005) Integrin alpha8beta1-fibronectin interactions promote cell survival via PI3 kinase pathway. Biochem Biophys Res Commun 329:305–311. https://doi.org/10.1016/j.bbrc.2005.01.125CrossRefPubMed

27.

Hartner A, Marek I, Cordasic N, Haas C, Schocklmann H, Hulsmann-Volkert G, Plasa I, Rascher W, Hilgers KF, Amann K (2008) Glomerular regeneration is delayed in nephritic alpha 8-integrin-deficient mice: contribution of alpha 8-integrin to the regulation of mesangial cell apoptosis. Am J Nephrol 28:168–178. https://doi.org/10.1159/000110022CrossRefPubMed

28.

Norman JT, Fine LG (1999) Progressive renal disease: fibroblasts, extracellular matrix, and integrins. Exp Nephrol 7:167–177. https://doi.org/10.1159/000020597CrossRefPubMed

29.

Volkert G, Jahn A, Dinkel C, Fahlbusch F, Zürn C, Hilgers KF, Rascher W, Hartner A, Marek I (2014) Contribution of the α8 integrin chain to the expression of extracellular matrix components. Cell Commun Adhes 21:89–98. https://doi.org/10.3109/15419061.2013.876012CrossRefPubMed

30.

Hartner A, Cordasic N, Rascher W, Hilgers KF (2009) Deletion of the alpha8 integrin gene does not protect mice from myocardial fibrosis in DOCA hypertension. Am J Hypertens 22:92–99. https://doi.org/10.1038/ajh.2008.309CrossRefPubMed

31.

Marek I, Volkert G, Jahn A, Fahlbusch F, Zürn C, Ozcan Z, Goppelt-Struebe M, Hilgers KF, Rascher W, Hartner A (2010) Lack of α8 integrin leads to morphological changes in renal mesangial cells, but not in vascular smooth muscle cells. BMC Cell Biol 11:102. https://doi.org/10.1186/1471-2121-11-102CrossRefPubMedPubMedCentral

32.

Zargham R, Touyz RM, Thibault G (2007) alpha 8 Integrin overexpression in de-differentiated vascular smooth muscle cells attenuates migratory activity and restores the characteristics of the differentiated phenotype. Atherosclerosis 195:303–312. https://doi.org/10.1016/j.atherosclerosis.2007.01.005CrossRefPubMed

33.

Marek I, Becker R, Fahlbusch FB, Menendez-Castro C, Rascher W, Daniel C, Volkert G, Hartner A (2018) Expression of the alpha8 integrin chain facilitates phagocytosis by renal mesangial cells. Cell Physiol Biochem 45:2161–2173. https://doi.org/10.1159/000488160CrossRefPubMed

Title: A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney
Authors: Ines Marek
Karl Friedrich Hilgers
Wolfgang Rascher
Joachim Woelfle
Andrea Hartner
Publication date: 01-12-2020
Publisher: Springer Berlin Heidelberg
Keyword: Glomerulonephritis
Published in: Molecular and Cellular Pediatrics / Issue 1/2020
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-020-00105-5

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A role for the alpha-8 integrin chain (itga8) in glomerular homeostasis of the kidney

Abstract

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Abstract

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