Processing of Laminin α Chains Generates Peptides Involved in Wound Healing and Host Defense

Laminins play a fundamental role in basement membrane architecture and function in human skin. The C-terminal laminin G domain-like (LG) modules of laminin α chains are modified by proteolysis to generate LG1–3 and secreted LG4–5 tandem modules. In this study, we provide evidence that skin-derived cells process and secrete biologically active peptides from the LG4–5 module of the laminin α3, α4 and α5 chain in vitro and in vivo. We show enhanced expression and processing of the LG4–5 module of laminin α3 in keratinocytes after infection and in chronic wounds in which the level of expression and further processing of the LG4–5 module correlated with the speed of wound healing. Furthermore, bacterial or host-derived proteases promote processing of laminin α3 LG4–5. On a functional level, we show that LG4–5-derived peptides play a role in wound healing. Moreover, we demonstrate that LG4-derived peptides from the