miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1

Abstract

Myocardial fibrosis after myocardial infarction (MI) is a leading cause of heart diseases. MI activates cardiac fibroblasts (CFs) and promotes CF to myofibroblast transformation (CMT). This study aimed to investigate the role of miR‐21 in the regulation of CMT and myocardial fibrosis. Primary rat CFs were isolated from young SD rats and treated with TGF‐β1, miR‐21 sponge or Jagged1 siRNA. Cell proliferation, invasion and adhesion were detected. MI model was established in male SD rats using LAD ligation method and infected with recombinant adenovirus. The heart function and morphology was evaluated by ultrasonic and histological analysis. We found that TGF‐β1 induced the up‐regulation of miR‐21 and down‐regulation of Jagged1 in rat CFs. Luciferase assay showed that miR‐21 targeted 3′‐UTR of Jagged1 in rat CFs. miR‐21 sponge inhibited the transformation of rat CFs into myofibroblasts, and abolished the inhibition of Jagged1 mRNA and protein expression by TGF‐β1. Furthermore, these effects of miR‐21 sponge on rat CFS were reversed by siRNA mediated knockdown of Jagged1. In vivo, heart dysfunction and myocardial fibrosis in MI model rats were partly improved by miR‐21 sponge but were aggravated by Jagged1 knockdown. Taken together, these results suggest that miR‐21 promotes cardiac fibroblast‐to‐myofibroblast transformation and myocardial fibrosis by targeting Jagged1. miR‐21 and Jagged1 are potential therapeutic targets for myocardial fibrosis.

Novel role of the clustered miR‐23b‐3p and miR‐27b‐3p in enhanced expression of fibrosis‐associated genes by targeting TGFBR3 in atrial fibroblasts

“…Meanwhile, the obvious increase of inflammatory factors, such as IL-1β and CRP, was also found in atrial appendage tissue of AF patients in the current study, which was supported by the previous reports. 28 Some miRNAs, such as miR-21 [12][13][14][15] and miR-26, 16,17 are involved in the modulation of atrial fibrosis. In this study, we demonstrated that miR-23b-3p and miR-27b-3p were increased in the human rheumatic atrial appendages and in Ang-II-induced HAFs.…”

“…For detection of mRNA expression of coding genes, the firststrand cDNA was generated from 1.5 μg total RNA using a mixture of oligo (dT) 15 and random primers with superscript reverse transcriptase (Invitrogen, Carlsbad, CA). Quantitative reversetranscription PCR (RT-qPCR) for miR-23b-3p and -27b-3p was performed on cDNA generated from 0.5 μg of total RNA according to the manufacturer's protocol (Ribobio, China).…”

miR‑26b inhibits isoproterenol‑induced cardiac fibrosis via the Keap1/Nrf2 signaling pathway

“…The present study demonstrated that miR-26b It has been thoroughly documented that miRNAs are involved in the development and progression of cardiac fibrosis. For example, Zhou et al (28) reported that miR-21 could promote cardiac fibroblast-to-myofibroblast transition by downregulating the expression of Jagged1. Moreover, several studies have indicated that the miR-26 family plays a central role in the development of cardiovascular disease by controlling critical signaling pathways or downstream gene targets.…”

Plasma microRNA: A novel non‑invasive biomarker for HBV‑associated liver fibrosis staging

“…In the present study, it was not determined whether hsa-miR-21 induction was a causative factor in fibrosis. However, a previous study revealed that increased hsa-miR-21 levels were associated with fibroblast dysfunction and fibrosis outcome (53). In a number of other organs, hsa-miR-21 is one of the most important miRNAs that is abundantly expressed following fibrosis induction (54)(55)(56).…”