MicroRNA-155 regulates myocardial fibrosis-related gene expression by targeting hypoxia-inducible factor 1α

  AIM  To investigate the effect and mechanism of microRNA-155 (miR-155) on the expressions of fibrosis-related genes in cardiac fibroblasts (CFs).

  METHODS  The mice were divided into 7 groups: control group, AngII group, Scramble group, miR-155 mimic group, AngII + Scramble group, AngII + miR-155 mimic group, and AngII + HIF-1α siRNA group. Angiotensin II (AngII) stimulated mouse CFs to simulate the activation of CFs during myocardial fibrosis. PCR and Western blot were used to detect the expressions of miR-155, type 1 collagen (Col 1), type 3 collagen (Col 3) and α-smooth muscle actin (α-SMA). Combination of miR-155 and 3’-untranslated region of hypoxia-inducible factor 1α (HIF-1α) was detected by dual luciferase reporter assay.

  RESULTS  AngII stimulation significantly promoted the expression of fibrosis-related genes in mouse CFs and decreased the level of miR-155. Over-expression of miR-155 significantly decreased the expression of fibrosis-related genes in mouse CFs induced by AngII. HIF-1α was negatively regulated by miR-155 and could bind to miR-155. miR-155 mimic and HIF-1α siRNA consistently reduced the expressions of fibrosis-associated proteins in mouse CFs.

  CONCLUSION  miR-155 can inhibit myocardial fibrosis. HIF-1α is a target gene of miR-155 and is involved in the process of miR-155 in inhibiting the expressions of CFs-related proteins and inhibiting myocardial fibrosis.