MicroRNA‐377 is up‐regulated and can lead to increased fibronectin production in diabetic nephropathy
- 18 August 2008
- journal article
- research article
- Published by Wiley in The FASEB Journal
- Vol. 22 (12), 4126-4135
- https://doi.org/10.1096/fj.08-112326
Abstract
Intrinsic glomerular cells in a diabetic milieu have transcriptional activation of genes that influence the development of diabetic nephropathy. The cellular repertoire of microRNAs can regulate translation of these expressed genes into proteins. Fibronectin is a key matrix protein accumulated in excess in diabetic nephropathy. Here, we exposed cultured human and mouse mesangial cells to high glucose and transforming growth factor-beta to simulate the diabetic milieu. In these conditions in vitro, as well as in mouse diabetic nephropathy models in vivo, microRNA-377 was consistently up-regulated relative to controls. Through a combination of computational and biological approaches, we identified relevant miR-377 target genes. Although fibronectin was induced by miR-377, it was not a direct target of miR-377. However, miR-377 led to reduced expressions of p21-activated kinase and superoxide dismutase, which enhanced fibronectin protein production. Thus, overexpression of miR-377 in diabetic nephropathy indirectly leads to increased fibronectin protein production; as such, miR-377 can have a critical role in the pathophysiology of this prevalent human disease.Keywords
Funding Information
- National Institutes of Health (R21DK057684, U24DK058820)
This publication has 48 references indexed in Scilit:
- miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130Proceedings of the National Academy of Sciences of the United States of America, 2008
- MEK1 activation by PAK: A novel mechanismCellular Signalling, 2007
- Protein Serine/Threonine Phosphatase PPM1A Dephosphorylates Smad1 in the Bone Morphogenetic Protein Signaling PathwayPublished by Elsevier BV ,2006
- PPM1A Functions as a Smad Phosphatase to Terminate TGFβ SignalingCell, 2006
- The PAK1 autoregulatory domain is required for interaction with NIK in Helicobacter pylori-induced NF-κB activationBiological Chemistry, 2006
- Superoxide dismutases and their impact upon human healthMolecular Aspects of Medicine, 2005
- A New Method for Large Scale Isolation of Kidney Glomeruli from MiceThe American Journal of Pathology, 2002
- Overexpression of Cu2+/Zn2+ Superoxide Dismutase Protects Against Early Diabetic Glomerular Injury in Transgenic MiceDiabetes, 2001
- Changes in Superoxide Dismutase Activities and Concentrations and Myeloperoxidase Activities in Leukocytes from Patients with Diabetes MellitusJournal of Diabetes and its Complications, 1999
- Complement regulation in the rat glomerulus: Crry and CD59 regulate complement in glomerular mesangial and endothelial cellsKidney International, 1995