Release of miR-29 target laminin C2 improves skin repair

Am J Pathol. 2023 Nov 17:S0002-9440(23)00422-4. doi: 10.1016/j.ajpath.2023.11.002. Online ahead of print.ABSTRACTMicroRNAs (miRs) are small non-coding RNAs that regulate mRNA targets in a cell-specific manner. miR-29 is expressed in mouse and human skin where it may regulate functions important for skin repair. Cutaneous wound healing model in miR29ab1 knockout (KO) mice was used to identify miR-29 targets in the wound matrix, where angiogenesis and maturation of provisional granulation tissue was enhanced in response to genetic deletion of miR-29. Consistently, antisense-mediated inhibition of miR-29 promoted angiogenesis in vitro by autocrine and paracrine mechanisms. These processes are likely to be mediated by miR-29 target mRNAs released upon removal miR-29 to improve cell-to-matrix adhesion. One of them, laminin C2 (also known as laminin γ2), was strongly upregulated during skin repair in the wound matrix of KO mice. Unexpectedly, Lamc2 deposited in basal membranes of endothelial cells of blood vessels forming in the granulation tissue of KO mice. New blood vessels showed punctate Lamc2-Itga6 interactions along the length of the proto-vessels, suggesting that higher levels of Lamc2 may contribute to the adhesion of endothelial cells, and thus assist angiogenesis within the wound. These findings are of likely translational relevance, as laminin C2 was deposited at the leading edge in human wounds, where it was forming a basal membrane for endothelial cells and assisting...
Source: Am J Pathol - Category: Pathology Authors: Source Type: research