Submitted on April 21, 2008
Revised on August 7, 2008
Accepted on August 26, 2008
Periostin induces proliferation of human autosomal dominant polycystic kidney cells through integrin alpha (v) receptor
Darren Paul Wallace1*, Megan A. Quante1, Gail A. Reif1, Emily Nivens1, Farhana Ahmed1, Scott J Hempson1, Gustavo Blanco2, and Tamio Yamaguchi1
1 Kansas University Medical Center
2 University of Kansas Medical Center
* To whom correspondence should be addressed. E-mail: dwallace{at}kumc.edu.
Progressive renal enlargement due to the growth of innumerable fluid-filled cysts is a central pathophysiologic feature of autosomal dominant polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge slowly and damage non-cystic parenchyma by mechanisms that have not been clearly defined. In a microarray analysis of cultured human ADPKD cyst epithelial cells, periostin mRNA was over expressed 15-fold compared to normal human kidney (NHK) cells. Periostin, initially identified in osteoblasts, is not expressed in normal adult kidneys but is expressed transiently during renal development. We found periostin in cyst-lining cells in situ, in extracellular matrix adjacent to the cysts and within cyst fluid. ADPKD cells secreted periostin across luminal and basolateral plasma membranes. Periostin increased proliferation of cyst epithelial cells 27.9 ± 3.1% (P < 0.001) above baseline and augmented in vitro cyst growth, but did not affect proliferation of normal renal cells. Expression of 
V-integrin, a periostin receptor, was 9-fold higher in ADPKD cells compared to NHK cells, and antibodies that block V-integrin inhibited periostin-induced cell proliferation. We conclude that periostin is a novel autocrine mitogen secreted by mural epithelial cells with the potential to accelerate cyst growth and promote interstitial remodeling in ADPKD.
