Dataset Information

MicroRNAs regulate renal tubule maturation through modulation of Pkd1.

ABSTRACT: MicroRNAs (miRNAs) contribute to the regulation of early kidney development, but their role during later stages of renal tubule maturation is not well understood. Here, we found that ablation of the miRNA-processing enzyme Dicer from maturing renal tubules produces tubular and glomerular cysts in mice. Inactivation of Dicer is associated with downregulation of miR-200, a kidney-enriched miRNA family, and upregulation of the polycystic kidney disease gene Pkd1. Inhibition of miR-200 in cultured renal epithelial cells disrupted tubulogenesis and led to upregulation of Pkd1. Using bioinformatic and in vitro approaches, we found that miR-200b/c/429 induce post-transcriptional repression of Pkd1 through two conserved binding sites in the 3'-Untranslated regions of Pkd1. Overexpression of PKD1 in renal epithelial cells was sufficient to disrupt tubulogenesis and produce cyst-like structures. In conclusion, miRNAs are essential for the maturation of renal tubules, and Pkd1 is a target of miR-200. These results also suggest that miRNAs may modulate PKD1 gene dosage and play a role in the initiation of cystogenesis.

SUBMITTER: Patel V

PROVIDER: S-EPMC3507362 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNAs regulate renal tubule maturation through modulation of Pkd1.

Patel Vishal V Hajarnis Sachin S Williams Darren D Hunter Ryan R Huynh Donovan D Igarashi Peter P

Journal of the American Society of Nephrology : JASN 20121108 12

MicroRNAs (miRNAs) contribute to the regulation of early kidney development, but their role during later stages of renal tubule maturation is not well understood. Here, we found that ablation of the miRNA-processing enzyme Dicer from maturing renal tubules produces tubular and glomerular cysts in mice. Inactivation of Dicer is associated with downregulation of miR-200, a kidney-enriched miRNA family, and upregulation of the polycystic kidney disease gene Pkd1. Inhibition of miR-200 in cultured r ...[more]

PMID: 23138483

Similar Datasets

Project description:Monocyte migration requires the dynamic redistribution of integrins through a regulated endo-exocytosis cycle, but the complex molecular mechanisms underlying this process have not been fully elucidated. Glia maturation factor-? (GMFG), a novel regulator of the Arp2/3 complex, has been shown to regulate directional migration of neutrophils and T-lymphocytes. In this study, we explored the important role of GMFG in monocyte chemotaxis, adhesion, and ?1-integrin turnover. We found that knockdown of GMFG in monocytes resulted in impaired chemotactic migration toward formyl-Met-Leu-Phe (fMLP) and stromal cell-derived factor 1? (SDF-1?) as well as decreased ?5?1-integrin-mediated chemoattractant-stimulated adhesion. These GMFG knockdown impaired effects could be reversed by cotransfection of GFP-tagged full-length GMFG. GMFG knockdown cells reduced the cell surface and total protein levels of ?5?1-integrin and increased its degradation. Importantly, we demonstrate that GMFG mediates the ubiquitination of ?1-integrin through knockdown or overexpression of GMFG. Moreover, GMFG knockdown retarded the efficient recycling of ?1-integrin back to the plasma membrane following normal endocytosis of ?5?1-integrin, suggesting that the involvement of GMFG in maintaining ?5?1-integrin stability may occur in part by preventing ubiquitin-mediated degradation and promoting ?1-integrin recycling. Furthermore, we observed that GMFG interacted with syntaxin 4 (STX4) and syntaxin-binding protein 4 (STXBP4); however, only knockdown of STXBP4, but not STX4, reduced monocyte migration and decreased ?1-integrin cell surface expression. Knockdown of STXBP4 also substantially inhibited ?1-integrin recycling in human monocytes. These results indicate that the effects of GMFG on monocyte migration and adhesion probably occur through preventing ubiquitin-mediated proteasome degradation of ?5?1-integrin and facilitating effective ?1-integrin recycling back to the plasma membrane.

Dataset Information

MicroRNAs regulate renal tubule maturation through modulation of Pkd1.

Publications

MicroRNAs regulate renal tubule maturation through modulation of Pkd1.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets