The characterization of alpha5-integrin expression on tubular epithelium during renal injury.
The hallmark of progressive chronic kidney disease is the deposition of extracellular matrix proteins and tubulointerstitial fibrosis. Integrins mediate cell-extracellular matrix interaction and may play a role tubular epithelial injury. Murine primary tubular epithelial cells (TECs) express alpha(5)-integrin, a fibroblast marker and the natural receptor for fibronectin. Microscopy localized alpha(5)-integrin on E-cadherin-positive cells, confirming epithelial expression. The expression of alpha(5)-integrin increased in TECs grown on fibronectin and occurred in parallel with an upregulation of alpha-smooth muscle actin (alphaSMA), a marker of epithelial-mesenchymal transition (EMT). Exposure of TECs to transforming growth factor (TGF)-beta also increased TEC alpha(5)-integrin expression in association with alphaSMA and EMT. Knock-down of alpha5-integrin expression with short interfering RNA attenuated the TGF-beta induction of alphaSMA but did not alter morphologic EMT. Rather, alpha5-integrin was necessary for epithelial cell migration on fibronectin but not type IV collagen during cell spreading and epithelial wound healing in vitro. Immunohistochemistry revealed basolateral tubular epithelial alpha(5)-integrin expression in mouse kidneys after unilateral ureteric obstruction but not in contralateral control kidneys. In patient biopsies of nondiabetic kidney disease, alpha(5)-integrin expression was increased significantly in the renal interstitium. Focal basolateral staining was also detected in injured, but not in normal, tubular epithelium. In summary, these data show that TECs are induced to express alpha(5)-integrin during EMT and tubular epithelial injury in vitro and in vivo. These results increase our understanding of the biology of integrins during EMT and tubular injury in chronic kidney disease.
White
Lindsay R
LR
University of Calgary, Alberta, T2N 4N1, Canada.
Blanchette
Jason B
JB
Ren
Li
L
Awn
Ali
A
Trpkov
Kiril
K
Muruve
Daniel A
DA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D004848:Epithelium / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039482:Integrin alpha5 / Q000096:biosynthesis* / Q000502:physiology; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014517:Ureteral Obstruction / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
D039482:Integrin alpha5; D016212:Transforming Growth Factor beta