Abstract
Left ventricular hypertrophy is an independent risk factor in diabetic patients. TGR5 is shown to express in hearts, but its functional role in diabetes-induced cardiac hypertrophy remained unclear. The current study investigated the role of TGR5 on high glucose-induced hypertrophy of H9C2 cells. After incubation with a high level of glucose, H9C2 cells showed hypertrophic responses. Activation of TGR5 by lithocholic acid (LCA) ameliorated cell hypertrophy and enhanced SERCA2a and phosphorylated phospholamban (PLN) expression in H9C2 cells. Triamterene inhibited these effects at an effective dose to block TGR5. However, LCA failed to modify the free radical elevation induced by high-glucose in the H9c2 cells. Moreover, PKA inhibitors, but not an Epac blocker, markedly improved hyperglycemia-induced hypertrophy and attenuated the increased SERCA2a expression by LCA; it also attenuated the phosphorylated PLN and SERCA2a protein expression levels in high glucose-treated H9C2 cells. In conclusion, TGR5 activation stimulated protein kinase A (PKA) to enhance PLN phosphorylation, which activated SERCA2a to remove Ca2+ from cytosol to sarcoplasmic reticulum in addition to the reduction of calcineurin/NFAT pathway signaling to ameliorate the hyperglycemia-induced cardiac hypertrophy shown in cardiomyocytes. TGR5 may service as a new target in the control of diabetic cardiomyopathy.
Highlights
Bile acids (BAs) have been introduced as the byproducts of cholesterol metabolism in liver to secret into the duodenum[1]
High-glucose treatment significantly increased in cardiomyocyte size compared to that of the normal group
Changes in biomarker levels for cardiac hypertrophy were assessed (Table 1); the results showed that atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP), and β-myosin heavy chain (β-MHC) mRNA levels changed in parallel
Summary
Bile acids (BAs) have been introduced as the byproducts of cholesterol metabolism in liver to secret into the duodenum[1]. Cardiac hypertrophy is introduced as an elevation in protein synthesis and/ or reactivation of the fetal gene program in cellular levels[8]. Calcineurinn dephosphorylated the nuclear factor of activated T-cells (NFAT) that may translocate into the nucleus to promote the gene expression, partly after forming a complex with GATA4. Calcineurin and NFAT are known for activation of the fetal gene program in response to hypertrophic stimuli, and they function as essential effectors during the formation of cardiac hypertrophy[9]. We used LCA to activate TGR5 and investigated the mechanism for alleviating the hyperglycemia-induced cardiac hypertrophy in cultured cardiac H9c2 cells. We used specific inhibitors to investigate the potential mediation of LCA-induced effects in H9c2 cells by PKA or Epac
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
