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This Article Full Text Full Text (PDF) All Versions of this Article: 295/4/F959    most recent 00559.2007v1 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 Google Scholar Articles by Saleem, M. A. Articles by Mathieson, P. W. PubMed PubMed Citation Articles by Saleem, M. A. Articles by Mathieson, P. W.

The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells

¹Academic and Children's Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; ²Albert Einstein Biotechnology Center and ³Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York; ⁴Universitätsklinikum Münster, Münster, Germany; and ⁵Division of Cell Biology, UCL Institute of Ophthalmology, London, United Kingdom

Submitted 26 November 2007 ; accepted in final form 25 July 2008

The glomerular podocyte is a highly specialized cell, with the ability to ultrafilter blood and support glomerular capillary pressures. However, little is known about either the genetic programs leading to this functionality or the final phenotype. We approached this question utilizing a human conditionally immortalized cell line, which differentiates from a proliferating epithelial phenotype to a differentiated form. We profiled gene expression during several time points during differentiation and grouped the regulated genes into major functional categories. A novel category of genes that was upregulated during differentiation was of smooth muscle-related molecules. We further examined the smooth muscle phenotype and showed that podocytes consistently express the differentiated smooth muscle markers smoothelin and calponin and the specific transcription factor myocardin, both in vitro and in vivo. The contractile contribution of the podocyte to the glomerular capillary is controversial. We demonstrated using two novel techniques that podocytes contract vigorously in vitro when differentiated and in real time were able to demonstrate that angiotensin II treatment decreases monolayer resistance, morphologically correlating with enhanced contractility. We conclude that the mature podocyte in vitro possesses functional apparatus of contractile smooth muscle cells, with potential implications for its in vivo ability to regulate glomerular dynamic and permeability characteristics.

mesenchyme; smoothelin; epithelial-mesenchymal transition; differentiation; development