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Roles of renal microRNA‐216a (miR‐216a) in TGF‐beta signaling and diabetic nephropathy
Author(s) -
Kato Mitsuo,
Wang Lin,
Wang Mei,
Yuan Hang,
Lanting Linda,
Putta Sumanth,
Todorov Ivan,
Zhang Jane,
Rossi John J,
Natarajan Rama
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.603.4
Subject(s) - diabetic nephropathy , downregulation and upregulation , medicine , transforming growth factor , endocrinology , microrna , chemistry , transforming growth factor beta , kidney , microbiology and biotechnology , biology , gene , biochemistry
Diabetic Nephropathy (DN) is a major microvascular complication of diabetes. Key features include accumulation of extracellular matrix (ECM) proteins such as collagen type1‐alpha 2 (Col1a2). Transforming growth factor‐beta 1 (TGF‐b), a key regulator of ECM genes, is increased in renal glomerular mesangial cells (MC) in DN. We recently found that miR‐192 levels were significantly enhanced in diabetic glomeruli, as well as TGF‐b‐treated MC. miR‐192 could target E‐box repressor Zeb2 and mediate TGF‐b‐induced Col1a2 expression. We now note that miR‐216a levels were also significantly enhanced in diabetic glomeruli and TGF‐b‐treated MC. miR‐216a could target YB‐1, an RNA‐binding protein (located in processing bodies), which regulates mRNA stability and translation. YB‐1 levels were reduced in diabetic glomeruli and TGF‐b‐treated MC. YB‐1‐TSC‐22 mRNA interaction was reduced by TGF‐b and also by miR‐216a or YB‐1 shRNA, while miR‐216a inhibitor increased this interaction. TSC‐22 protein levels were enhanced by TGF‐b due to reduced YB‐1. Since TSC‐22 is known to augment TGF‐b signaling via Smad3/4, these data suggest that TGF‐b induced miR‐216a and TSC‐22 translation due to reduced YB‐1 can enhance Col1a2 expression. These results uncover novel roles for renal miRs in controlling TGF‐b‐induced Col1a2. miRs could be novel targets for diabetic vascular diseases. Supported by NIH (NIDDK) and JDRF.