title: The molecular and functional phenotype of glomerular podocytes reveals key features of contractile smooth muscle cells.
abstract: 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.
authors.affiliation: Academic and Children's Renal Unit, University of Bristol, Lifeline Bldg., Southmead Hospital, Bristol, BS10 5NB, United Kingdom. m.saleem@bristol.ac.uk
authors.forename: Moin A
authors.initials: MA
authors.lastname: Saleem
authors.forename: Jiri
authors.initials: J
authors.lastname: Zavadil
authors.forename: Maryse
authors.initials: M
authors.lastname: Bailly
authors.forename: Karen
authors.initials: K
authors.lastname: McGee
authors.forename: Ian R
authors.initials: IR
authors.lastname: Witherden
authors.forename: Hermann
authors.initials: H
authors.lastname: Pavenstadt
authors.forename: Hsianghao
authors.initials: H
authors.lastname: Hsu
authors.forename: Julia
authors.initials: J
authors.lastname: Sanday
authors.forename: Simon C
authors.initials: SC
authors.lastname: Satchell
authors.forename: Rachel
authors.initials: R
authors.lastname: Lennon
authors.forename: Lan
authors.initials: L
authors.lastname: Ni
authors.forename: Erwin P
authors.initials: EP
authors.lastname: Bottinger
authors.forename: Peter
authors.initials: P
authors.lastname: Mundel
authors.forename: Peter W
authors.initials: PW
authors.lastname: Mathieson
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology; D000804:Angiotensin II / Q000494:pharmacology; D002454:Cell Differentiation / Q000502:physiology; D002461:Cell Line, Transformed; D048430:Cell Shape / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology; D020869:Gene Expression Profiling; D006801:Humans; D008648:Mesoderm / Q000166:cytology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D050199:Podocytes / Q000166:cytology* / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D000099251:Myocardin
chemical_list: D000804:Angiotensin II; D009687:Nuclear Proteins; D015534:Trans-Activators; D014662:Vasoconstrictor Agents; D000099251:Myocardin