Hydrogen sulfide ameliorates rat myocardial fibrosis induced by thyroxine through PI3K/AKT signaling pathway

Abstract

This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (HS) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with HS intervention (TH + HS group) and the normal group with HS intervention (HS group). Pathological changes were observed via H&E staining and Masson staining, Expressions of MMPs/TIMPs, PI3K/AKT, autophagy-related proteins in myocardial tissues were detected via Western blotting, and the expressions of miR-21, miR-34a, miR-214 and miR-221 were detected via RT-qPCR. Compared with the control group, in the TH group, myocardial fibrosis was more significant, the expressions of proteins in PI3K/AKT and autophagy-related proteins were significantly decreased, as well as the expression of miR-221; while the expressions of miR-21, miR-34a and miR-214 were significantly elevated. By contrast, all above-mentioned changes were obviously reversed with HS treatment, which demonstrated the positive function of HS in amelioration of rat myocardial fibrosis induced by thyroxine. The mechanism of such amelioration may be correlated with autophagy activated by the upregulation of expression of PI3K/AKT signaling pathway and downregulation of expressions of miR-21, miR-34a and miR-214.

miR-214-3p Attenuates Sepsis-Induced Myocardial Dysfunction in Mice by Inhibiting Autophagy through PTEN/AKT/mTOR Pathway

“…Yang et al [ 25 ] reported that miRNA-214 suppresses oxidative stress in diabetic nephropathy via the ROS/Akt/mTOR signaling pathway and uncoupling protein2. Liu et al reported that miR-214 could regulate autophagy through the PI3K/AKT signalling pathway in the rat model of myocardial fibrosis [ 26 ]. Gong et al reported that Oridonin relieved hypoxia-caused apoptosis and autophagy via adjusting the PI3K/AKT/mTOR pathway through the enhancement of miR-214 in H9C2 cells.…”

MicroRNAs as Potential Pharmaco-Targets in Ischemia-Reperfusion Injury Compounded by Diabetes

“…Although a role in autophagy has not been reported for miR-21, it appears to protect against cardiac I/R injury by its ability to inhibit excessively augmented autophagic pathways [116]. Consistent with the potential synergy between miR-146 and miR-21, it was recently reported that upregulation of miR-21 is associated with decreased autophagy in myocardial tissues [117].…”

Exogenous Hydrogen Sulfide Ameliorates Diabetic Myocardial Fibrosis by Inhibiting Cell Aging Through SIRT6/AMPK Autophagy

“…CSE is the key enzyme of endogenous H 2 S source in cardiovascular system ( Zheng et al., 2018 ), CBS and 3MST also participate in the production of endogenous H 2 S in peripheral vascular tissue ( Prabhudesai et al., 2018 ). Our research group has confirmed that H 2 S could antagonize myocardial fibrosis by regulating multiple intracellular signaling pathways ( Liu et al., 2018a ; Liu et al., 2018b ), however the internal regulatory mechanism of H 2 S is very complex, which is still not clear until now. Therefore, it is of great significance to further explore the myocardial protection mechanism of H 2 S. This study observed that exogenous H 2 S can activate endogenous H 2 S-producing enzyme CSE and improve STZ-induced myocardial fibrosis and MMPs/TIMP1 imbalance in diabetic rats.…”