Dataset Information

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.

SUBMITTER: Saleem MA

PROVIDER: S-EPMC2576149 | biostudies-literature | 2008 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Saleem Moin A MA Zavadil Jiri J Bailly Maryse M McGee Karen K Witherden Ian R IR Pavenstadt Hermann H Hsu Hsianghao H Sanday Julia J Satchell Simon C SC Lennon Rachel R Ni Lan L Bottinger Erwin P EP Mundel Peter P Mathieson Peter W PW

American journal of physiology. Renal physiology 20080806 4

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 ...[more]

PMID: 18684887

Similar Datasets

Project description:IntroductionHydrochlorothiazide has a negative influence on penile erection but little is known about the mechanism(s) involved.AimsTo characterize the effects of this diuretic on mouse corpus cavernosum (CC) smooth muscle in vitro and ex vivo.MethodsCC strips of C57BL/6 mice (12-16 weeks old) were mounted in organ baths containing Krebs-Henseleit solution and tissue reactivity was evaluated. Expression of genes encoding diuretic targets and enzymes involved in penile erection were evaluated by polymerase chain reaction.Main outcome measuresStimulation-response curves to phenylephrine (10 nmol/L-100 ?mol/L) or to electrical field stimulation (1-32 Hz) were constructed, with or without hydrochlorothiazide. Strips of CC from mice after long-term hydrochlorothiazide treatment (6 mg/kg/day for 4 weeks) with or without amiloride (0.6 mg/kg/day for 4 weeks) in vivo also were studied. Nitric oxide and Rho-kinase pathways were evaluated.ResultsHydrochlorothiazide (100 ?mol/L) increased the maximum response to phenylephrine by 64% in vitro. This effect was unaffected by the addition of indomethacin (5 ?mol/L) but was abolished by N((?))-nitro-L-arginine methyl ester (100 ?mol/L). Hydrochlorothiazide (100 ?mol/L) potentiated electrical field stimulation-induced contraction in vitro, but not ex vivo. Long-term treatment with hydrochlorothiazide increased the maximum response to phenylephrine by 60% and resulted in a plasma concentration of 500 ± 180 nmol/L. Amiloride (100?mol/L) caused rightward shifts in concentration-response curves to phenylephrine in vitro. Long-term treatment with hydrochlorothiazide plus amiloride did not significantly increase the maximum response to phenylephrine (+13%). Reverse transcriptase polymerase chain reaction did not detect the NaCl cotransporter in mouse CC. Hydrochlorothiazide did not change Rho-kinase activity, whereas amiloride decreased it in vitro and ex vivo (approximately 18% and 24% respectively). A 40% decrease in Rock1 expression also was observed after long-term treatment with hydrochlorothiazide plus amiloride.ConclusionHydrochlorothiazide potentiates contraction of smooth muscle from mouse CC. These findings could explain why diuretics such as hydrochlorothiazide are associated with erectile dysfunction.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets