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Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1.

Publication ,  Journal Article
Lee, K; Boctor, S; Barisoni, LMC; Gusella, GL
Published in: Journal of the American Society of Nephrology : JASN
April 2015

Dysregulation of polycystin-1 (PC1) leads to autosomal dominant polycystic kidney disease (ADPKD), a disorder characterized by the formation of multiple bilateral renal cysts, the progressive accumulation of extracellular matrix (ECM), and the development of tubulointerstitial fibrosis. Correspondingly, cystic epithelia express higher levels of integrins (ECM receptors that control various cellular responses, such as cell proliferation, migration, and survival) that are characteristically altered in cystic cells. To determine whether the altered expression of ECM and integrins could establish a pathologic autostimulatory loop, we tested the role of integrin-β1 in vitro and on the cystic development of ADPKD in vivo. Compared with wild-type cells, PC1-depleted immortalized renal collecting duct cells had higher levels of integrin-β1 and fibronectin and displayed increased integrin-mediated signaling in the presence of Mn(2+). In mice, conditional inactivation of integrin-β1 in collecting ducts resulted in a dramatic inhibition of Pkd1-dependent cystogenesis with a concomitant suppression of fibrosis and preservation of normal renal function. Our data provide genetic evidence that a functional integrin-β1 is required for the early events leading to renal cystogenesis in ADPKD and suggest that the integrin signaling pathway may be an effective therapeutic target for slowing disease progression.

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Published In

Journal of the American Society of Nephrology : JASN

DOI

EISSN

1533-3450

ISSN

1046-6673

Publication Date

April 2015

Volume

26

Issue

4

Start / End Page

888 / 895

Related Subject Headings

  • Urology & Nephrology
  • TRPP Cation Channels
  • Polycystic Kidney Diseases
  • Mice
  • Kidney
  • Integrin beta1
  • Fibrosis
  • Cell Line
  • Animals
  • 3202 Clinical sciences
 

Citation

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Lee, K., Boctor, S., Barisoni, L. M. C., & Gusella, G. L. (2015). Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1. Journal of the American Society of Nephrology : JASN, 26(4), 888–895. https://doi.org/10.1681/asn.2013111179
Lee, Kyung, Sylvia Boctor, Laura M. C. Barisoni, and G Luca Gusella. “Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1.Journal of the American Society of Nephrology : JASN 26, no. 4 (April 2015): 888–95. https://doi.org/10.1681/asn.2013111179.
Lee K, Boctor S, Barisoni LMC, Gusella GL. Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1. Journal of the American Society of Nephrology : JASN. 2015 Apr;26(4):888–95.
Lee, Kyung, et al. “Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1.Journal of the American Society of Nephrology : JASN, vol. 26, no. 4, Apr. 2015, pp. 888–95. Epmc, doi:10.1681/asn.2013111179.
Lee K, Boctor S, Barisoni LMC, Gusella GL. Inactivation of integrin-β1 prevents the development of polycystic kidney disease after the loss of polycystin-1. Journal of the American Society of Nephrology : JASN. 2015 Apr;26(4):888–895.

Published In

Journal of the American Society of Nephrology : JASN

DOI

EISSN

1533-3450

ISSN

1046-6673

Publication Date

April 2015

Volume

26

Issue

4

Start / End Page

888 / 895

Related Subject Headings

  • Urology & Nephrology
  • TRPP Cation Channels
  • Polycystic Kidney Diseases
  • Mice
  • Kidney
  • Integrin beta1
  • Fibrosis
  • Cell Line
  • Animals
  • 3202 Clinical sciences