Role of IRE1α in regulating miRNA34a in high glucose-induced cardiomyocyte hypertrophy

  AIM  To study the role of inositol-requiring enzyme1 α (IRE1 α) gene in cardiomyocyte hypertrophy induced by high glucose and its relationship with miRNA34a.

  METHODS  Cardiomyocytes were isolated and cultured. They were divided into different groups: a control group, a high glucose overexpression IRE1α group, and s control IRE1α group (Con Ad-IRE1α). IRE1α adenovirus was used to interfere with these cells to observe the effects of high glucose on cardiomyocyte viability, hypertrophy, and the expression of atrial natriuretic peptide (ANP). Western blot was used to detect the expression of ANP and IRE1α. qRT-PCR was utilized to detect the expression of ANP, IRE1α, and miRNA34a. Immunofluorescence staining was utilized to detect cell purity and cross-sectional area.

  RESULTS  Compared with the control group, with the increase of glucose concentration, the cell viability continued to decrease, the expression of ANP increased, the expression of IRE1α gene and protein decreased, and the glucose concentration reached a lowest level of 30 mmol/L. Compared with the control group, high glucose decreased the cell viability, stimulated the expression of ANP and increased the cross sectional area of the cardiomyocytes (P < 0.05), while over-expression of IRE1α gene significantly up-regulated the levels of cell viability of cardiomyocytes. The expression of ANP protein and gene decreased and hypertrophy of cardiomyocytes was inhibited in the high glucose culture (P < 0.05). In addition, qRT-PCR results showed that miRNA34a expression gradient increased with the increase of high glucose concentration and miRNA34a expression decreased significantly after over-expression of IRE1α gene.

  CONCLUSION  Over-expression of IRE1α gene effectively inhibits hypertrophy induced by high glucose and its mechanism may be related to down-regulation of miRNA34a expression.