Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease.

Periostin overexpression in collecting ducts accelerates renal cyst growth and fibrosis in polycystic kidney disease. Am J Physiol Renal Physiol. 2018 Oct 17;: Authors: Raman A, Parnell SC, Zhang Y, Reif GA, Dai Y, Khanna A, Daniel E, White C, Vivian JL, Wallace DP Abstract In polycystic kidney disease (PKD), persistent activation of cell proliferation and matrix production contributes to cyst growth and fibrosis, leading to progressive deterioration of renal function. Previously, we showed that periostin, a matricellular protein involved in tissue repair, is overexpressed by cystic epithelial cells of PKD kidneys. Periostin binds αVβ3-integrins and activates integrin-linked kinase (ILK), leading to Akt/mTOR-mediated proliferation of human PKD cells. By contrast, periostin does not stimulate the proliferation of normal human kidney cells. This difference in the response to periostin is due to elevated expression of αVβ3-integrins by cystic cells. To determine if periostin accelerates cyst growth and fibrosis, we generated mice with conditional overexpression of periostin in the collecting ducts (CD). Ectopic CD expression of periostin was not sufficient to induce cyst formation or fibrosis in wildtype mice. However, periostin overexpression in pcy/pcy ( pcy) kidneys significantly increased mTOR activity, cell proliferation, cyst growth, and interstitial fibrosis; and accelerated the decline in renal function. Moreover, CD-specifi...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research