Repression of let-7 by Transforming Growth Factor-β1-induced Lin28 up-regulates collagen expression in glomerular mesangial cells under diabetic conditions.

Repression of let-7 by Transforming Growth Factor-β1-induced Lin28 up-regulates collagen expression in glomerular mesangial cells under diabetic conditions. Am J Physiol Renal Physiol. 2014 Oct 29;:ajprenal.00458.2014 Authors: Park JT, Kato M, Lanting L, Castro N, Nam BY, Wang M, Kang SW, Natarajan R Abstract Accumulation of mesangial extracellular matrix (ECM) proteins such as collagen type 1-α2 (col1a2) and type 4-α1 (col4a1) is a key feature of diabetic nephropathy (DN). Transforming growth factor-β1 (TGF-β) plays important roles in ECM accumulation in DN, and evidence shows a mediatory role for microRNAs (miRNAs). Here we found that miRNA let-7 family members (let-7b/c/d/g/i) were down-regulated in TGF-β-treated mouse mesangial cells (MMC) along with up-regulation of col1a2 and col4a1. Ectopic expression of let-7b in TGF-β-treated MMCs attenuated the col1a2 and col4a1 up-regulation. Conversely, let-7b inhibitors increased col1a2 and col4a1 levels. Co-transfection of MMCs with mouse col1a2 or col4a1 3'-UTR luciferase constructs and let-7b inhibitors increased luciferase activity. However, constructs with let-7 target site mutations were un-responsive to TGF-β. TGF-β induced 3'UTR activity was attenuated by let-7b mimics, suggesting col1a2 and col4a1 are direct targets of let-7b. In addition, Lin28b, a negative regulator of let-7 biogenesis, was up-regulated in TGF-β-treated MMCs. Luciferase assays sh...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research

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Source: Journal of Musculoskeletal Neuronal Interactions - Category: Neurology Tags: J Musculoskelet Neuronal Interact Source Type: research
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Source: Diabetes Mine - Category: Endocrinology Authors: Source Type: blogs
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Source: Frontiers in Endocrinology - Category: Endocrinology Source Type: research
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Source: mobihealthnews - Category: Information Technology Source Type: news
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Source: NIH Funding Opportunities (Notices, PA, RFA) - Category: Research Source Type: funding
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