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

Diabetic nephropathy (DN) is a common cause of chronic kidney disease and end-stage renal disease, which can be triggered by oxidative stress. In this study, we investigated the renoprotective effect of the ethyl acetate extract of Salvia miltiorrhiza (EASM) on DN and examined the underlying molecular mechanism. We observed that EASM treatment attenuated metabolic abnormalities associated with hyperglycemic conditions in the experimental DN model. In streptozotocin (STZ)-induced mice, EASM treatment reduced albuminuria, improved renal function and alleviated the pathological alterations within the glomerulus. To mimic the hyperglycemic conditions in DN patients, we used high glucose (25[Formula: see text]mmol/L) media to stimulate mouse mesangial cells (MMCs), and EASM inhibited high glucose-induced reactive oxygen species. We also observed that EASM enhanced the expression of nuclear factor erythroid-2-related factor 2 (Nrf2), which mediated the anti-oxidant response, and its downstream gene heme oxygenase-1 (HO-1) and NAD(P)H quinone dehydrogenase 1 (NQO1) with concomitant decrease of expression of kelch-like ECH-associated protein 1 (keap1) both in vitro and in vivo. Taken together, these results suggest that EASM alleviates the progression of DN and this might be associated with activation of Nrf2.
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PMID:Salvia miltiorrhiza Lipophilic Fraction Attenuates Oxidative Stress in Diabetic Nephropathy through Activation of Nuclear Factor Erythroid 2-Related Factor 2. 2894 66

c-Jun N-terminal kinase (JNK) contributes to the pathogenesis of diabetic nephropathy (DN). The JNK inhibitor SP600125 was reported to ameliorate DN. However, the mechanism remained unclear. We previously reported that SP600125 activated nuclear factor erythroid 2-related factor 2 (NRF2), a governor of the cellular antioxidant defense system, in the aortas of the diabetic mice. Given the critical role of NRF2 in preventing DN, the present study aimed to test whether or not NRF2 is required for SP600125's protection against DN. To test the role of NRF2 in SP600125's effect, streptozotocin-induced C57BL/6 wild-type (WT) and Nrf2-knockout (KO) diabetic mice were treated in the presence or absence of SP600125, for 24 weeks. To explore the mechanism by which SP600125 activates NRF2, mouse mesangial cells (MMCs) were treated with high glucose (HG), in the presence or absence of either SP600125 or JNK siRNA. SP600125 significantly attenuated the diabetes-induced renal oxidative stress, inflammation, fibrosis, pathological change and dysfunction in the WT, but not the Nrf2 KO mice. SP600125 inactivated JNK, inhibited kelch-like ECH-associated protein 1 expression, preserved NRF2 protein and facilitated its nuclear translocation in the kidneys of the WT mice, the effects of which were similarly produced by either SP600125 or JNK siRNA in HG-treated MMCs. Further, both SP600125 and JNK siRNA alleviated HG-induced mesangial oxidative stress and expression of inflammatory and fibrotic genes. The present study demonstrates that NRF2 is required for SP600125's protection against DN. SP600125 activates NRF2 possibly via inhibition of JNK-induced Keap1 expression.
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PMID:SP600125 suppresses Keap1 expression and results in NRF2-mediated prevention of diabetic nephropathy. 2927 84