Regulation of Semaphorin3A in the process of cutaneous wound healing

Abstract

Semaphorin 3A (Sema3A) has been recognized as a crucial regulator of morphogenesis and homeostasis over a wide range of organ systems. However, its function in cutaneous wound healing is poorly understood. In our study, we demonstrated that Sema3A adenovirus plasmids transfection limited keratinocyte proliferation and decreased migrative capacity as assessed by in vitro wound healing assay. Sema3A transduction inhibited TGF-β1-mediated keratinocyte migration and EMT process. Besides, we applied mice with K14-Cre-mediated deletion of Sema3A and found that Sema3A depletion postponed wound closure with decreased re-epithelialization and matrix growth. Contrary to the results obtained with full-length Sema3A plasmids transfection, increased keratinocyte migration with recombinant Sema3A proteins resulted in quicker closure of the wounding area after a scratch. Further, exogenously applied recombinant Sema3A worked with EGF to maintain the activation of EGFR by interacting with NRP1 and thereby regulated the internalization of the EGFR-NRP1 complex. Taken together, these results indicated a paradoxical role of autonomous and non-autonomous Sema3A expression during wound healing. Combined administration of recombinant EGF and Sema3A proteins could accelerate the process of wound repair, thus providing promising treatment prospects in the future.

LncRNA MALAT1 in Keratinocyte function: A review of recent advances

“…In the context of keratinocytes, EMT is involved in various biological processes, including wound healing, tissue repair, and skin regeneration [ 45 ]. During wound healing, keratinocytes at the wound edge undergo EMT to acquire a more migratory and invasive phenotype, allowing them to move into the wound site and contribute to tissue repair [ 46 ]. This transition is essential for the re-epithelialization of the wound and the restoration of the skin barrier [ 47 ].…”

Endothelial Robo4 suppresses endothelial-to-mesenchymal transition induced by irradiation and improves hematopoietic reconstitution

“…Several studies have unanimously demonstrated that the TGF-β isoforms play a potential role in End-MT induction [ 13 , 14 ]. Upon binding TGF-β ligands to their receptors, they recruit and phosphorylate several cytoplasmic molecules, most notably the Smad2/3 and Smad1/5 proteins, which bind with Smad4 protein to form a complex [ 15 , 16 ]. The resulting transcription factor heterocomplex translocates into the nucleus, interacting with other transcription factors such as Snail, Snug, Twist, and Zeb1 to regulate gene expression in the End-MT [ 17 , 18 ].…”