Fig. 1

Mechanical cue-dependent scarring. a TGF-β activates fibroblasts to transform into myofibroblasts and the latter give rise to α-SMA, endowing wound aberrant contraction force. b Epithelial-mesenchymal transition (EMT) in inflammatory environment causes fibrosis related gene expression through diverse pathways. RAS-responsive element binding protein 1 (RREB1) serves as a connector between MAPK and Smad pathways. c Inflammatory factors leak from damaged vascular endothelium; imbalance between growth and regression of neovascularization causes irregular vessel cluster; blood flow in irregular vessel produces aberrant shear stress. d Nerve damage within wound launches neurogenic inflammation where neuropeptides [calcitonin gene-related peptide (CGRP) and substance P] from nerve endings mediate harmful vascular events including abnormal vasodilation and plasm extravasation. e Neutrophiles and macrophages, as the main innate immunocytes within wound, upregulate inflammatory factors and provide fibroblasts with enduring activating signals. Created with BioRender.com. TGF-β transforming growth factor-β, α-SMA α-smooth muscle actin, ST2 suppression of tumorigenicity 2 receptor, PI3K/Akt phosphatidylinositol-3-kinase/Akt, MAPK mitogen-activated protein kinase, TFs transcriptional factors, ZEB1 zinc finger E-box binding homeobox 1, ZEB2 zinc finger E-box binding homeobox 2, IL11 interleukin-11, CTGF connective tissue growth factor, PDGF-B platelet-derived growth factor B, WISP1 Wnt1-inducible signaling pathway protein 1, NF-κB nuclear factor-κB, STAT3 signal transducer and activator or transcription 3, HIF-1α hypoxia-inducible factor-1α