miR-214 and Its Primary Transcript Dnm3os Regulate Fibrosis and Inflammation Through RAGE Signaling in Diabetic Kidney Disease.

Unlabelled: Pathologic signaling via the receptor for advanced glycation end products (RAGE) is critical to diabetic kidney disease (DKD) development, whereas RAGE deletion is renoprotective. Noncoding RNAs (ncRNAs), including miRNAs, also play key roles in DKD, including in renal fibrosis. However, the involvement of ncRNAs in RAGE signaling remains unclear.

Cells of NG2 lineage increase in glomeruli of mice following podocyte depletion.

Under certain circumstances, podocytes can be partially replaced following their loss in disease. The inability of podocytes to proliferate suggests that replacement derives from other cell types. Because neural/glial antigen 2 (NG2)-expressing cells can serve as progenitors in other organs and because herein we showed increased NG2 staining in podocytes following their loss in experimental focal segmental glomerulosclerosis, we used lineage tracing in NG2-CreER tdTomato mice to test the hypothesis that partial podocyte replacement might derive from this cell population.

RAGE Deletion Confers Renoprotection by Reducing Responsiveness to Transforming Growth Factor-β and Increasing Resistance to Apoptosis.

Signaling via the receptor of advanced glycation end products (RAGE)-though complex and not fully elucidated in the setting of diabetes-is considered a key injurious pathway in the development of diabetic nephropathy (DN). We report here that RAGE deletion resulted in increased expression of fibrotic markers (collagen I and IV, fibronectin) and the inflammatory marker MCP-1 in primary mouse mesangial cells (MCs) and in kidney cortex. RNA sequencing analysis in MCs from RAGE and wild-type mice confirmed these observations.

Charting the transcriptional landscape of cells of renin lineage following podocyte depletion.

Renin producing cells of the juxtaglomerulus, herein called cells of renin lineage (CoRL), have garnered recent interest for their propensity to act as a progenitor source for various kidney cell types including podocytes. Despite recent advances, the process of transdifferentiation of CoRL to podocytes is poorly understood. In this study, we employed a transgenic reporter mouse line which permanently labels CoRL with ZsGreen fluorescent protein, allowing for isolation by fluorescence-activated cell sorting.

miR-21 promotes renal fibrosis in diabetic nephropathy by targeting PTEN and SMAD7.

The cytokine transforming growth factor (TGF)-β1 plays a central role in diabetic nephropathy (DN) with data implicating the miRNA (miR) miR-21 as a key modulator of its prosclerotic actions. In the present study, we demonstrate data indicating that miR-21 up-regulation positively correlates with the severity of fibrosis and rate of decline in renal function in human DN. Furthermore, concomitant analyses of various models of fibrotic renal disease and experimental DN, confirm tubular miR-21 up-regulation.

Study of microRNA in diabetic nephropathy: isolation, quantification and biological function.

In recent years, several studies have reported dysregulation of microRNA expression in disease with a growing interest focussed on targeting microRNAs as a novel therapy for human disease. This is especially true in diabetic nephropathy where the expression of several microRNAs is dysregulated, contributing to the increased expression and accumulation of extracellular matrix proteins and increased pro-fibrotic signalling, ultimately resulting in renal fibrosis. The development of various techniques and microRNA reagents has enabled work to progress very rapidly in this area.

Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b.

Renal fibrosis results from excessive accumulation of extracellular matrix mainly driven by transforming growth factor-β1 (TGF-β1). Certain microRNAs have been implicated in this disease, and here we examine the role of let-7b. Rat proximal tubular epithelial cells (NRK52E) were treated with TGF-β1 for 3 days to assess the expression of markers of fibrosis and let-7b.

microRNA in the development of diabetic complications.

Today's world population is currently faced with a new type of non-transmissible pandemic: obesity. This lifestyle-related condition is driving the emergence of the diabetes pandemic through the development of low-level chronic inflammation. In recent years, a novel class of non-coding RNA, microRNA (miRNA), have emerged as being important regulators of numerous biological functions.