title: Protective Effects of Berberine on Renal Injury in Streptozotocin (STZ)-Induced Diabetic Mice.
abstract: Diabetic nephropathy (DN) is a serious diabetic complication with renal hypertrophy and expansion of extracellular matrices in renal fibrosis. Epithelial-to-mesenchymal transition (EMT) of renal tubular epithelial cells may be involved in the main mechanism. Berberine (BBR) has been shown to have antifibrotic effects in liver, kidney and lung. However, the mechanism of cytoprotective effects of BBR in DN is still unclear. In this study, we investigated the curative effects of BBR on tubulointerstitial fibrosis in streptozotocin (STZ)-induced diabetic mice and the high glucose (HG)-induced EMT in NRK 52E cells. We found that BBR treatment attenuated renal fibrosis by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway in the diabetic kidneys. Further revealed that BBR abrogated HG-induced EMT and oxidative stress in relation not only with the activation of Nrf2 and two Nrf2-targeted antioxidative genes (NQO-1 and HO-1), but also with the suppressing the activation of TGF-β/Smad signaling pathway. Importantly, knockdown Nrf2 with siRNA not only abolished the BBR-induced expression of HO-1 and NQO-1 but also removed the inhibitory effect of BBR on HG-induced activation of TGF-β/Smad signaling as well as the anti-fibrosis effects. The data from present study suggest that BBR can ameliorate tubulointerstitial fibrosis in DN by activating Nrf2 pathway and inhibiting TGF-β/Smad/EMT signaling activity.
authors.affiliation: Department of Nephrology, Benxi Center Hospital, 29 Victory Road, Benxi 117000, Liaoning, China. zhang2013_11@163.com.|Science Experiment Center, Benxi Center Hospital, Benxi 117000, Liaoning, China. zhang2013_11@163.com.|Key Laboratory of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang 110001, Liaoning, China. zhang2013_11@163.com.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Science Experiment Center, Benxi Center Hospital, Benxi 117000, Liaoning, China. lnbxwxf@yeah.net.
authors.forename: Hui
authors.initials: H
authors.lastname: He
authors.affiliation: Troops of 95935 Unit, Haerbin 150111, Heilongjiang, China. dl7711@163.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Liang
authors.affiliation: Science Experiment Center, Benxi Center Hospital, Benxi 117000, Liaoning, China. zhang2013_12@163.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Science Experiment Center, Benxi Center Hospital, Benxi 117000, Liaoning, China. liangbixiang@sohu.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liang
authors.affiliation: Department of pathophysiology, China Medical University, Shenyang 110001, Liaoning, China. chizhihong2015@126.com.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Chi
authors.affiliation: Department of Nephrology, the First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, China. jfeima@sohu.com.
authors.forename: Jianfei
authors.initials: J
authors.lastname: Ma
mesh_terms: D000818:Animals; D001599:Berberine / Q000627:therapeutic use*; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000188:drug therapy / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D013311:Streptozocin / Q000633:toxicity; D016212:Transforming Growth Factor beta / Q000378:metabolism
chemical_list: D051267:NF-E2-Related Factor 2; D016212:Transforming Growth Factor beta; D001599:Berberine; D013311:Streptozocin
keywords: EMT; Nrf2 pathway; TGF-β/Smad signaling pathway; berberbine; diabetic nephropathy; renal tubular epithelial cells