SALL4 mediates SHP2 inhibition in myocardial fibroblasts through the DOT1L/H3K79me2 signaling pathway to promote the progression of myocardial infarction.

Objective: To explore the influence of SALL4 in cardiac fibroblasts on the progression of myocardial infarction.

Methods: Analysis of genes specifically expressed in myocardial infarction by bioinformatics methods; The impact of SALL4 on myocardial infarction was assessed using mouse ultrasound experiments and Masson staining; The effect of SALL4 on the expression levels of collagen-I and collagen-III in myocardial tissue was examined by immunohistochemical staining; The migration ability of cardiac fibroblasts was evaluated using a Transwell assay; The proliferative ability of cardiac fibroblasts was tested using a CCK-8 assay; The relative fluorescence intensity of α-SMA and CTGF in cardiac fibroblasts were checked through immunofluorescence staining experiment; The expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, α-SMA, CTGF, and PAI-1 in myocardial tissues or cardiac fibroblasts was detected using western blot analysis.

Results: SALL4-specific high expression in myocardial infarction; SALL4 intensified the alterations in the heart structure of mice with myocardial infarction and worsened the fibrosis of myocardial infarction; SALL4 also promoted the expression of SALL4, DOT1L, H3K79me2, P53, SHP2, YAP, nucleus-YAP, collagen-I, collagen-III, α-SMA, CTGF, and PAI-1 in myocardial infarction tissues and cardiac fibroblasts; Subsequently, SALL4 could enhance the immunofluorescence intensity of α-SMA and CTGF; Moreover, SALL4 could promote the proliferation and migration of cardiac fibroblasts.

Conclusion: In cardiac fibroblasts, SALL4 mediates the DOT1L/H3K79me2 signaling pathway to inhibit SHP2, which then promotes the YAP/TAZ signaling pathway, thereby facilitating the progression of myocardial infarction.