title: Emodin suppresses hyperglycemia-induced proliferation and fibronectin expression in mesangial cells via inhibiting cFLIP.
abstract: As one of the most serious microvascular complications of diabetes and a major cause of end stage renal disease, diabetic nephropathy (DN) is calling for effective treatment strategies. Here, we provide evidence that hyperglycemia can induce proliferation and decreasing apoptosis of mesangial cells (MCs) and subsequent renal dysfunction by up-regulating cellular FLICE-inhibitory protein (cFLIP). Treatment with emodin significantly turns down the accelerated cell cycle and proliferation of MCs cultured in high glucose (HG) via inhibiting cFLIP. In vitro, knockdown of cFLIP can arrest cell cycle and accelerate cell death by activating caspase-8, caspase-3 and caspase-9, and down-regulate proliferating cell nuclear antigen (PCNA). Our results also suggest that emodin regulates cFLIP expression in transcriptional level. Importantly, emodin lessens proteinuria and fibronectin expression in early-stage of streptozotocin (STZ)-induced diabetic rats. These findings demonstrate that emodin represent a promising strategy to prevent renal dysfunction in early-stage of diabetes mellitus.
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Junjie
authors.initials: J
authors.lastname: Gao
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Fangli
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Weisong
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Su
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Canghui
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Nephrology, Cangzhou Central Hospital, Cangzhou, China.
authors.forename: Shuyi
authors.initials: S
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000209:etiology / Q000235:genetics; D004642:Emodin / Q000008:administration & dosage*; D005353:Fibronectins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000473:pathology; D050527:Mesangial Cells / Q000378:metabolism / Q000473:pathology; D051381:Rats; D051437:Renal Insufficiency / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D005353:Fibronectins; D004642:Emodin