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Therefore, calpain promotes remodeling of the actin cytoskeleton in VSMCs to form podosomes by activating PKC, accompanied by the degradation of extracellular matrix (ECM) ( 2+ activates the ERK1/2-Egr-1 signaling pathway and form a cascade amplification effect, thereby participating in nicotine-induced smooth muscle cell proliferation ( Nicotine also participates in the functional and phenotypic changes of smooth muscle cells through nAChR-induced regulation of multiple related downstream signaling pathways