Figure 5.

Inhibition of the TGFB1 regulatory network in the infarct zone of the early moderate exercise‐trained heart. (I) The upstream analysis of the integrated ingenuity pathway analysis between miRNAs and mRNAs in the infarct zone predicted that compared with the sedentary MI heart, the primary upstream molecule was TGFB1, which was inhibited in the infarct zone of the early moderate exercise MI heart (P‐value = 1.78E‐08; z‐score = −2.266). The inhibition of 10 genes (TGFB1, FN1, MAPK14, SP1, SP3, ESR1, SMAD4, EGR1, CREBBP and SMAD3) and the activation of 3 genes (HDAC2, TP73 and SMAD7) played a role in the inhibition of the TGFB1 regulatory network. The network displays the regulatory relationship of these 13 genes in which SP1, SMAD4 and SMAD3, the direct downstream genes that are regulated by TGFB1, were inhibited, whereas SMAD7, the inhibitor of the TGFB1 pathway, was activated. In addition, the indirect downstream genes, FN1, MAPK14, SP3, ESR1, EGR1 and CREBBP, were predicted to be inhibited, whereas TP73 was activated. (II) The qPCR quantifications of the expression levels of selected genes included in the TGFB1 network. The animals were trained on early moderate exercise for two weeks beginning one day after MI. n = 3 per group. *P < .05 vs the sedentary group