Objective
Current study focused on the influence of miR‐200b‐3p on cardiocyte apoptosis of diabetic cardiomyopathy (DCM) by regulating CD36 and peroxisome proliferator‐activated receptor γ (PPAR‐γ) signaling pathway.
Methods
Bioinformatic analysis was used to analyze differentially expressed microRNA (miRNAs), messenger RNAs (mRNAs) and activated pathways in DCM. And then quantitative real‐time polymerase chain reaction (qRT‐PCR) was conducted to verify expression of miR‐200b‐3p and CD36 in DCM model rats and glucose treated H9c2 cell line. Luciferase reporter assay was used to verify the transcriptional regulation of agomiR‐200b‐3p and investigate the relationship between miR‐200b‐3p and CD36. Flow cytometry was performed to assess cardiocyte apoptosis in different interference conditions. Echocardiography was used to illustrate the ejection fraction rate and fraction shortening rate of DCM model rats. Next, hematoxylin‐eosin (H&E) staining assay was carried out to reveal structures of cardiocyte tissues with transfection in different conditions. Masson trichrome staining was used to evaluate myocardial fibrosis. Western blot analysis was used to detect the expression levels of PPAR‐γ signaling‐related protein PPAR‐γ and Bcl‐2.
Results
miR‐200b‐3p was low‐expressed while CD36 was overexpressed in DCM. AgomiR‐200b‐3p could inhibit the expression of CD36 to regulate cardiocyte apoptosis in DCM. CD36 activated PPAR‐γ signaling pathway in DCM. Silencing CD36 or GW9662 treatment protect rat against DCM.
Conclusion
miR‐200b‐3p targeted CD36 to regulate cardiocyte apoptosis of DCM by activating PPAR‐γ signaling pathway.
Abstract5-methylcytosine (m5C) modification, which is mainly induced by the RNA methyltransferase NSUN2 (NOP2/Sun domain family, member 2), is an important chemical posttranscriptional modification in mRNA and has been proven to play important roles in the progression of many cancers. However, the functions and underlying molecular mechanisms of NSUN2-mediated m5C in osteosarcoma (OS) remain unclear. In this study, we found NSUN2 was highly expressed in OS tissues and cells. We also discovered that higher expression of NSUN2 predicted poorer prognosis of OS patients. Our study showed that NSUN2 could promote the progression of OS cells. Moreover, we employed RNA sequencing, RNA immunoprecipitation (RIP), and methylated RIP to screen and validate the candidate targets of NSUN2 and identified FABP5 as the target. We observed that NSUN2 stabilized FABP5 mRNA by inducing m5C modification and further promoted fatty acid metabolism in OS cells. Moreover, both knocking down the expression of FABP5 and adding fatty acid oxidation inhibitor could counterbalance the promoting effect of NSUN2 on the progression of OS. Our study confirms that NSUN2 can up-regulate the expression of FABP5 by improving the stability of FABP5 mRNA via m5C, so as to promote fatty acid metabolism in OS cells, and finally plays the role in promoting the progression of OS. Our findings suggest that NSUN2 is a promising prognostic marker for OS patients and may serve as a potential therapeutic target for OS treatment.
Application of extracorporeal circuits and indwelling medical devices has saved many lives. However, it is accompanied with two major complications: thrombosis and infection. To address this issue, we apply therapeutic nitric oxide gas (NO) and antibacterial peptide for synergistically tailoring such devices for surface anti-thrombogenic and antifouling dual functions. Such functional surface is realized by stepwise conjugation of NO-generating compound of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelated copper ions (Cu-DOTA) and dibenzylcyclooctyne- (DBCO-) modified antimicrobial peptide based on carbodiimide and click chemistry respectively. The integration of peptide and Cu-DOTA grants the modified surface the ability to not only efficiently inhibit bacterial growth, but also catalytically generate NO from endogenous s-nitrosothiols (RSNO) to reduce adhesion and activation of platelets, preventing the formation of thrombus. We envision that the stepwise synergistic modification strategy by using anticoagulant NO and antibacterial peptide would facilitate the surface multifunctional engineering of extracorporeal circuits and indwelling medical devices, with reduced clinical complications associated with thrombosis and infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.