title: Integrins in kidney disease.
abstract: A major hallmark of chronic kidney injury is fibrosis, which is characterized by increased accumulation of extracellular matrix components that replace the damaged tissue. Normally, the synthesis and degradation of extracellular matrix components are finely regulated; however, when matrix replacement goes unchecked, there is unwanted and irreversible tissue scarring with consequent organ damage, organ failure, and, in certain cases, death. Many factors, including cell-matrix interactions, play a role in the development of renal fibrosis. Cell-matrix interactions are made possible by integrins, a family of transmembrane receptors that, upon binding to the extracellular matrix, activate intracellular signaling. Thus, they control various cell functions, including survival, proliferation, migration, and matrix homeostasis. Genetic mutations in humans and the development of animal models lacking integrins in selective parts of the kidney have improved our understanding of molecular mechanisms and pathways controlling matrix remodeling in kidney disease. Here we outline the major integrins involved in kidney disease and some of the major molecular mechanisms whereby integrins contribute to kidney fibrosis.
authors: Division of Nephrology, Vanderbilt University Medical Center, Nashville, TN 27232, USA. ambra.pozzi@vanderbilt.edu
authors: Ambra
authors: A
authors: Pozzi
authors: Roy
authors: R
authors: Zent
mesh_terms: D002450:Cell Communication / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism*; D005355:Fibrosis; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D016023:Integrins
references: Am J Pathol. 2002 Mar;160(3):861-7
references: 11891185
references: Pediatr Nephrol. 2012 Jun;27(6):891-900
references: 21603909
references: Am J Pathol. 2011 Feb;178(2):609-20
references: 21281793
references: J Clin Invest. 2012 Jan;122(1):348-58
references: 22201679
references: Am J Med Genet A. 2004 Oct 1;130A(2):138-45
references: 15372515
references: Am J Pathol. 2004 Aug;165(2):617-30
references: 15277235
references: Nat Genet. 1996 Jul;13(3):370-3
references: 8673141
references: Cell. 1997 Mar 7;88(5):603-13
references: 9054500
references: Cell. 2002 Sep 20;110(6):673-87
references: 12297042
references: Dev Biol. 2008 Jan 15;313(2):584-93
references: 18082680
references: Int Immunol. 2012 Apr;24(4):219-32
references: 22298882
references: Kidney Int. 2012 Jun;81(11):1086-97
references: 22297672
references: Fibrogenesis Tissue Repair. 2010 Sep 22;3:19
references: 20860797
references: J Clin Invest. 2006 Aug;116(8):2272-9
references: 16886065
references: J Clin Invest. 2012 Dec;122(12):4375-87
references: 23114595
references: Nephron Clin Pract. 2008;108(3):c169-75
references: 18277079
references: Dev Biol. 2008 Apr 15;316(2):288-301
references: 18328474
references: Matrix Biol. 2000 Aug;19(4):319-23
references: 10963992
references: Am J Pathol. 2000 Nov;157(5):1649-59
references: 11073824
references: Development. 2009 Mar;136(5):843-53
references: 19176588
references: J Cell Sci. 1999 Feb;112 ( Pt 3):263-72
references: 9885280
references: J Cell Biol. 2001 Jul 23;154(2):447-58
references: 11470831
references: J Cell Biol. 2006 Oct 9;175(1):33-9
references: 17015618
references: Am J Med Genet A. 2005 Sep 15;138(1):73-4
references: 16097004
references: Curr Opin Nephrol Hypertens. 2012 Jul;21(4):428-32
references: 22569341
references: J Biol Chem. 2010 Dec 17;285(51):40114-24
references: 20940300
references: Am J Physiol Renal Physiol. 2010 Nov;299(5):F1151-7
references: 20826576
references: Nat Med. 2008 Jan;14(1):55-63
references: 18084301
references: Annu Rev Med. 2013;64:357-66
references: 23190150
references: J Am Soc Nephrol. 2012 Jun;23(6):1027-38
references: 22440900
references: Development. 1996 Nov;122(11):3537-47
references: 8951069
references: N Engl J Med. 2012 Apr 19;366(16):1508-14
references: 22512483
references: Development. 2007 Jul;134(13):2501-9
references: 17537792
references: J Am Soc Nephrol. 2008 Apr;19(4):677-84
references: 18235087
references: Development. 2006 Mar;133(5):967-75
references: 16452099
references: Mol Cell Biol. 2010 Jun;30(12):3048-58
references: 20368353
references: Am J Pathol. 2003 Oct;163(4):1261-73
references: 14507636
references: Blood. 2004 Oct 15;104(8):2217-23
references: 15265795
references: Am J Kidney Dis. 2000 Jul;36(1):190-6
references: 10873890
references: Am J Pathol. 2007 Jan;170(1):110-25
references: 17200187
references: Mol Cell Biol. 2007 May;27(9):3313-26
references: 17339338
references: Hum Mol Genet. 2004 Nov 1;13(21):2625-32
references: 15367484
references: Am J Pathol. 2002 Oct;161(4):1265-72
references: 12368200
references: Exp Cell Res. 2012 May 15;318(9):1001-10
references: 22417893
references: Kidney Int. 2003 Jul;64(1):119-27
references: 12787402
references: Nat Med. 2011 Jul 31;17(8):952-60
references: 21804539
references: J Biol Chem. 2012 Oct 12;287(42):35139-35152
references: 22888006