机构：[1]Hebei Univ Chinese Med, Shijiazhuang, Hebei, Peoples R China[2]Hebei Key Lab Integrat Med Liver Kidney Patterns, Shijiazhuang, Hebei, Peoples R China[3]Hebei Univ Chinese Med, Hosp 1, Shijiazhuang, Hebei, Peoples R China[4]Hebei Med Univ, Hosp 3, Shijiazhuang, Hebei, Peoples R China[5]Hebei Univ Chinese Med, Hosp 2, Shijiazhuang, Hebei, Peoples R China
The present study was undertaken to investigate the therapeutic effect and underlying mechanisms of lumbrokinase (LK) on diabetic kidney disease (DKD). Kidney tissue samples from DKD patients and normal controls were collected from hospitals. The type 2 diabetic nephropathy model was induced in db/db mice. The mice were then randomly divided into a model group (DM group) and an LK group. db/m mice were used as the control group (Con group). After 12 weeks of treatment with LK (234 KU/kg/day), biochemical parameters were tested, and pathological changes in the kidney were observed under a light microscope. The epithelial-to-mesenchymal transition (EMT), mRNA m6A methylation proteins, and activated TGF-beta 1/Smad pathway components were assessed by western blot or immunofluorescence in DKD patients, model mice, and high glucose-stimulated HK-2 cells. We found that the m6A eraser METTL3 was expressed at low levels in DKD patients, model mice, and high glucose-stimulated HK-2 cells. METTL3 overexpression reversed the high glucose-induced activation of the TGF-beta 1/Smad pathway and EMT through snail in vitro. However, LK can restore the expression of the m6A-modifying enzyme METTL3 in vivo and in vitro, suppressed EMT, and alleviated renal interstitial fibrosis by downregulating snail. Overall, LK ameliorated renal fibrosis through the regulation of Snail via m6A RNA METTL3.
基金：
Hebei Province Natural Science Foundation; Hebei Province Key RD Projects [223777150D]; Hebei Provincial Administration of Traditional Chinese Medicine Scientific Research Program [2024102]; Medical Science Research Project of Hebei Provincial Health Commission [20230213]; [H2022423320]; [H2022423342]
第一作者机构：[1]Hebei Univ Chinese Med, Shijiazhuang, Hebei, Peoples R China[2]Hebei Key Lab Integrat Med Liver Kidney Patterns, Shijiazhuang, Hebei, Peoples R China
共同第一作者：
通讯作者：
通讯机构：[1]Hebei Univ Chinese Med, Shijiazhuang, Hebei, Peoples R China[2]Hebei Key Lab Integrat Med Liver Kidney Patterns, Shijiazhuang, Hebei, Peoples R China[5]Hebei Univ Chinese Med, Hosp 2, Shijiazhuang, Hebei, Peoples R China
推荐引用方式(GB/T 7714)：
Yang Fan,Zhang Xiaoyun,Huang Jiaan,et al.Lumbrokinase (LK) ameliorates diabetic kidney disease renal fibrosis through regulating snail via m6A RNA methyltransferase 3[J].SCIENTIFIC REPORTS.2024,14(1):doi:10.1038/s41598-024-80168-w.
