Peng Zhao1, Xiaqiu Li1, Yang Li2, Jiaying Zhu3, Yu Sun4, Jianli Hong5. 1. Department of Nephrology, Haining People's Hospital, No. 2, Qianjiang West Road, Haizhou Street, Haining, 314400, Zhejiang, China. 2. Department of General Medicine, Haining People's Hospital, Haining, 314400, Zhejiang, China. 3. Department of Endocrinology, Haining People's Hospital, Haining, 314400, Zhejiang, China. 4. Department of Nephrology, Haining People's Hospital, No. 2, Qianjiang West Road, Haizhou Street, Haining, 314400, Zhejiang, China. sunyuzhejiang@126.com. 5. Department of Endocrinology, Hengdian Wenrong Hospital, 99 Yingbin Road, Dongyang, 322118, Zhejiang, China. pwtew3rt@21cn.com.
Abstract
PURPOSE: Diabetic nephropathy (DN) is one of the most serious complications of diabetes that leads to decline of renal function. Although numerous studies have revealed that microRNAs (miRNAs) play essential roles in the progression of DN, whether miR-365 is involved remains elusive. METHODS: The successful construction of DN model was confirmed by ELSIA, hematoxylin-eosin (HE) and Masson staining assay. The expression of miR-365 was detected through RT-qPCR. The levels of BDNF, p-TrkB, α-smooth muscle actin (SMA), collagen IV (Col.IV), transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were evaluated by western blot, IF or ELISA assays. Luciferase reporter assay was used to detect the interaction between miR-365 and BDNF. RESULTS: The DN mice model was induced by streptozotocin (STZ). Then miR-365 expression was found to upregulate in tissues of DN rat. Furthermore, elevated expression of miR-365 was found in high glucose (HG)-treated HK-2 cells. Silencing of miR-365 suppressed the accumulation of ECM components and secretion of inflammatory cytokines in HK-2 cells. In addition, it was demonstrated that miR-365 could target BDNF. The protein levels of BDNF and p-TrkB were negatively regulated by miR-365 in HK-2 cells. Moreover, inhibition of miR-365 suppressed the levels of SMA, Col.IV, TGF-β1, TNF-α, and IL-6, indicating the renal fibrosis was inhibited by miR-365 knockdown. CONCLUSION: MiR-365 could regulate BDNF-TrkB signal axis in STZ induced DN fibrosis and renal function. The results of the current study might provide a promising biomarker for the treatment of DN in the future.
PURPOSE: Diabetic nephropathy (DN) is one of the most serious complications of diabetes that leads to decline of renal function. Although numerous studies have revealed that microRNAs (miRNAs) play essential roles in the progression of DN, whether miR-365 is involved remains elusive. METHODS: The successful construction of DN model was confirmed by ELSIA, hematoxylin-eosin (HE) and Masson staining assay. The expression of miR-365 was detected through RT-qPCR. The levels of BDNF, p-TrkB, α-smooth muscle actin (SMA), collagen IV (Col.IV), transforming growth factor-β1 (TGF-β1), tumor necrosis factor α (TNF-α), and interleukin-6 (IL-6) were evaluated by western blot, IF or ELISA assays. Luciferase reporter assay was used to detect the interaction between miR-365 and BDNF. RESULTS: The DN mice model was induced by streptozotocin (STZ). Then miR-365 expression was found to upregulate in tissues of DN rat. Furthermore, elevated expression of miR-365 was found in high glucose (HG)-treated HK-2 cells. Silencing of miR-365 suppressed the accumulation of ECM components and secretion of inflammatory cytokines in HK-2 cells. In addition, it was demonstrated that miR-365 could target BDNF. The protein levels of BDNF and p-TrkB were negatively regulated by miR-365 in HK-2 cells. Moreover, inhibition of miR-365 suppressed the levels of SMA, Col.IV, TGF-β1, TNF-α, and IL-6, indicating the renal fibrosis was inhibited by miR-365 knockdown. CONCLUSION: MiR-365 could regulate BDNF-TrkB signal axis in STZ induced DN fibrosis and renal function. The results of the current study might provide a promising biomarker for the treatment of DN in the future.
Authors: M J Hoch; M T Bruno; A Faustin; N Cruz; L Crandall; T Wisniewski; O Devinsky; T M Shepherd Journal: AJNR Am J Neuroradiol Date: 2019-01-31 Impact factor: 3.825
Authors: Ying Fan; Xuezhu Li; Wenzhen Xiao; Jia Fu; Ray C Harris; Maja Lindenmeyer; Clemens D Cohen; Nicolas Guillot; Margaret H Baron; Niansong Wang; Kyung Lee; John C He; Detlef Schlondorff; Peter Y Chuang Journal: Diabetes Date: 2015-01-09 Impact factor: 9.461