FIGURE 2.

Main Mechanotransduction Signaling Pathways in keloid. TGF-β/Smad, integrin/FAK, YAP/TAZ signaling pathways and Calcium ion signaling are the main mechanotransduction signaling pathways that mediate mechanoresponsiveness. TGF-β senses mechanical forces and signals through Smads, where Smad2/3 binds to Smad4 and enters the nucleus, where they bind DNA and initiate trans-activation of target genes. Integrin signaling induces gene expression through FAK/Erk pathway, and also interferes with TGF-β/Smad signaling pathway. Mechanical stimulation can promote YAP to nuclear transfer and function. The Gq-coupled receptor activated by stretch stimulation can activate PLCβ and produce DAG and IP3. IP3 acts on the intracellular calcium pool to release Ca²⁺, resulting in the increase of intracellular free calcium ion concentration and the subsequent intracellular reaction of Raf/MEK/Erk pathway.