Your browser doesn't support javascript.
loading
MicroRNA-29a Attenuates Diabetic Glomerular Injury through Modulating Cannabinoid Receptor 1 Signaling.
Tung, Chun-Wu; Ho, Cheng; Hsu, Yung-Chien; Huang, Shun-Chen; Shih, Ya-Hsueh; Lin, Chun-Liang.
Afiliação
  • Tung CW; Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. p122219@cgmh.org.tw.
  • Ho C; Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. p122219@cgmh.org.tw.
  • Hsu YC; Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. libra@cgmh.org.tw.
  • Huang SC; Division of Endocrinology and Metabolism, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. libra@cgmh.org.tw.
  • Shih YH; Department of Nephrology, Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. hc1238@cgmh.org.tw.
  • Lin CL; Kidney and Diabetic Complications Research Team (KDCRT), Chang Gung Memorial Hospital, Chiayi 61363, Taiwan. hc1238@cgmh.org.tw.
Molecules ; 24(2)2019 Jan 11.
Article em En | MEDLINE | ID: mdl-30642005
Diabetic nephropathy often leads to end-stage renal disease and life-threatening morbidities. Simple control of risk factors is insufficient to prevent the progression of diabetic nephropathy, hence the need for discovering new treatments is of paramount importance. Recently, the dysregulation of microRNAs or the cannabinoid signaling pathway has been implicated in the pathogenesis of various renal tubulointerstitial fibrotic damages and thus novel therapeutic targets for chronic kidney diseases have emerged; however, the role of microRNAs or cannabinoid receptors on diabetes-induced glomerular injuries remains to be elucidated. In high-glucose-stressed renal mesangial cells, transfection of a miR-29a precursor sufficiently suppressed the mRNA and protein expressions of cannabinoid type 1 receptor (CB1R). Our data also revealed upregulated CB1R, interleukin-1ß, interleukin-6, tumor necrosis factor-α, c-Jun, and type 4 collagen in the glomeruli of streptozotocin (STZ)-induced diabetic mice, whereas the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) was decreased. Importantly, using gain-of-function transgenic mice, we demonstrated that miR-29a acts as a negative regulator of CB1R, blocks the expressions of these proinflammatory and profibrogenic mediators, and attenuates renal hypertrophy. We also showed that overexpression of miR-29a restored PPAR-γ signaling in the renal glomeruli of diabetic animals. Collectively, our findings indicate that the interaction between miR-29a, CB1R, and PPAR-γ may play an important role in protecting diabetic renal glomeruli from fibrotic injuries.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / MicroRNAs / Receptor CB1 de Canabinoide / Nefropatias Diabéticas / Glomérulos Renais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Transdução de Sinais / MicroRNAs / Receptor CB1 de Canabinoide / Nefropatias Diabéticas / Glomérulos Renais Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Ano de publicação: 2019 Tipo de documento: Article