Decreased activity of forkhead box protein O1 (FoxO1) may fail to inhibit ASMC proliferation and collagen synthesis; its function is regulated by phosphorylation via the AKT pathway, and sustained AKT activation in COPD leads to FoxO1 inactivation.HIF-1α is highly expressed in ASMCs, enhancing glucose uptake by upregulating GLUT1, inducing glycolytic enzyme expression, and inhibiting PDH activity to prevent pyruvate entry into the TCA cycle — providing energy and biosynthetic precursors for ASMC proliferation and myofibroblast differentiation (32, 35, 38). This evidence concerns the gene FOXO1 and chronic obstructive pulmonary disease.