Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mesenchymal stem cells (MSCs) are shown to alleviate renal injury of diabetic nephropathy (DN) in rats. However, the underlying mechanism of this beneficial effect is not fully understood. The aims of this study are to evaluate effects of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on renal cell apoptosis in streptozotocin- (STZ-) induced diabetic rats and explore the underlying mechanisms. Characteristics of UC-MSCs were identified by flow cytometry and differentiation capability. Six weeks after DN induction by STZ injection in Sprague-Dawley rats, the DN rats received UC-MSCs once a week for consecutive two weeks. DN-related physical and biochemical parameters were measured at 2 weeks after UC-MSC infusion. Renal histological changes were also assessed. Moreover, the apoptosis of renal cells and expression of apoptosis-related proteins were evaluated. Compared with DN rats, rats treated with UC-MSCs showed suppressed increase in 24-hour urinary total protein, urinary albumin to creatinine ratio, serum creatinine, and blood urea nitrogen. UC-MSC treatment ameliorated pathological abnormalities in the kidney of DN rats as evidenced by H&E, PAS, and Masson Trichrome staining. Furthermore, UC-MSC treatment reduced apoptosis of renal cells in DN rats. UC-MSCs promoted expression of antiapoptosis protein Bcl-xl and suppressed expression of high mobility group protein B1 (HMGB1) in the kidney of DN rats. Most importantly, UC-MSCs suppressed upregulation of thioredoxin-interacting protein (TXNIP), downregulation of thioredoxin 1 (TRX1), and activation of apoptosis signal-regulating kinase 1 (ASK1) and P38 MAPK in the kidney of DN rats. Our results suggest that UC-MSCs could alleviate nephrocyte injury and albuminuria of DN rats through their antiapoptotic property. The protective effects of UC-MSCs may be mediated by inhibiting TXNIP upregulation in part.
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PMID:Umbilical Cord-Derived Mesenchymal Stem Cells Ameliorate Nephrocyte Injury and Proteinuria in a Diabetic Nephropathy Rat Model. 3240 7

The dysregulated long noncoding RNAs (lncRNAs) are associated with the pathogenesis of diabetic nephropathy (DN). LncRNA potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1) plays an important role in diabetes, but the role and mechanism of KCNQ1OT1 in DN are largely unknown. Serum samples were collected from 30 DN patients and normal volunteers. High glucose (HG)-challenged human mesangial cells (HMCs) were used as a cell model of DN. KCNQ1OT1, microRNA-18b (miR-18b), and high mobility group protein A2 (HMGA2) abundances were examined via quantitative reverse transcription polymerase chain reaction or western blot. Cell proliferation was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide. Oxidative stress was assessed via the levels of reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and SOD2. Extracellular matrix (ECM) accumulation was investigated by the levels of fibronectin (FN), collagen I (Col I), and Col IV. The relationship between miR-18b and KCNQ1OT1 or HMGA2 was determined via dual-luciferase reporter analysis, RNA immunoprecipitation, and pull-down. KCNQ1OT1 expression was increased and miR-18b expression was decreased in DN patients and HG-challenged HMCs. miR-18b was targeted via KCNQ1OT1. Knockdown of KCNQ1OT1 weakened HG-caused proliferation, oxidative stress, and ECM accumulation of HMCs by increasing miR-18b. HMGA2 was targeted via miR-18b. miR-18b alleviated HG-induced cell proliferation, oxidative stress, and ECM accumulation by decreasing HMGA2. Silence of KCNQ1OT1 reduced HMGA2 expression via miR-18b. KCNQ1OT1 knockdown attenuated HG-induced proliferation, oxidative stress, and ECM accumulation of HMCs by regulating miR-18b/HMGA2 axis.
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PMID:KCNQ1OT1/miR-18b/HMGA2 axis regulates high glucose-induced proliferation, oxidative stress, and extracellular matrix accumulation in mesangial cells. 3298 27