Astragaloside IV inhibits cardiac fibrosis via miR-135a-TRPM7-TGF-β/Smads pathway. - GreenMedInfo Summary

ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac fibrosis is a common characteristic of many cardiac diseases. Our previous results showed that TRPM7 channel played an important role in the fibrosis process. MicroRNA-135a was reported to get involved in the fibrotic process. As one of the active ingredients of Astragalus membranaceus (Fisch.) Bunge, Astragaloside IV (ASG) has been showed the cardiac fibrosis inhibition via various mechanism, while no data suggest its action related to miRNAs regulation.

AIM OF THE STUDY: The objective of this article is to investigate the inhibition effect of Astragaloside IV on cardiac fibrosis through the miR-135a-TRPM7-TGF-β/Smads pathway.

MATERIALS AND METHODS: We used isoproterenol (ISO) to induce cardiac fibrosis in vivo and in vitro. SD rats were treated with ISO (5 mg/kg/day) subcutaneously (s.c.) for 14 days, and ASG (10 mg/kg/d) was given p.o. from the 6th day of the modeling. Cardiac fibroblasts (CFs) of neonatal rats were incubated with ISO (10 μM) and treated with ASG (10 μM) simultaneously for 24 h.

RESULTS: The results showed that ASG treatment could significantly decrease the current and protein expression of TRPM7 which was proved as one target of miR-135a. The activation of TGF-β/Smads pathway was suppressed and the expression of α-SMA and Collagen I were also decreased obviously. In addition, we proved that there was a positive feedback between the activation of TGF-β/Smads pathway and the elevation of TRPM7, both of which could promote the development of myocardial fibrosis.

CONCLUSIONS: All these findings suggested that ASG inhibited cardiac fibrosis by targeting the miR-135a-TRPM7-TGF-β/Smads pathway.