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This Article Full Text Full Text (PDF) All Versions of this Article: 295/5/F1463    most recent 90266.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (1) Citing Articles via Google Scholar Google Scholar Articles by Wallace, D. P. Articles by Yamaguchi, T. Search for Related Content PubMed PubMed Citation Articles by Wallace, D. P. Articles by Yamaguchi, T.

Periostin induces proliferation of human autosomal dominant polycystic kidney cells through _V-integrin receptor

¹Kidney Institute and Departments of ²Medicine and ³Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas

Submitted 21 April 2008 ; accepted in final form 26 August 2008

Progressive renal enlargement due to the growth of innumerable fluid-filled cysts is a central pathophysiological feature of autosomal dominant polycystic kidney disease (ADPKD). These epithelial neoplasms enlarge slowly and damage noncystic parenchyma by mechanisms that have not been clearly defined. In a microarray analysis of cultured human ADPKD cyst epithelial cells, periostin mRNA was overexpressed 15-fold compared with 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 the 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 ninefold higher in ADPKD cells compared with 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.

polycystic kidney disease; ADPKD; extracelluar matrix; interstitial filrosis; epithelial