1462 Expression and function of laminin extracellular matrix in wound repair

Abstract

Extracellular matrix plays critical roles in wound repair and tissue regeneration. Laminins are major non-collagenous extracellular components in the basement membrane (BM) of skin dermal-epidermal junction and microvascular blood vessels. In this study we used a porcine burn wound model to explore the expression and functions of laminins and some important dermal matrix proteins and regulators in wound repair. Swine were used for our animal model since their skin is morphologically similar to human skin. Fresh skin burn wound samples from 6 young female pigs were collected at days 0, 1, 4, 7, 10, 14 and 21 post wounding. mRNA expressions were analyzed using reverse transcription and polymerase chain reactions with gene specific primers. The results showed that: 1) marked induction of gene expression for epidermal BM reconstitution: the expressions of both major epidermal BM laminins, -332 and -511, were significantly increased shortly after wounding, with laminin511 the highest and lasted longer, with peak at day 7 and day 10 for laminin332 and laminin511, respectively; a marked increase of type IV collagen mRNA level peaked at day 1 and remained high over the course; 2) strong induction of gene expression for dermal restoration: the expression of blood vessel BM laminin411 increased shortly after wounding and reached peak at day 4; a significantly delayed induction of types I and III collagen expression was observed (from 10 days post wounding) compared with excisional wounds; the induction of elastin expression occurred at later stage of healing, 21 days post wounding; 3) increased expression of matrix metalloproteinases (MMP) for tissue remodeling: a striking increased expression of MMP1 and MMP9 was observed shortly after wounding and lasted through entire experiment; the marked induction of TIMP1, a tissue inhibitor of MMP, occurred shortly after wounding and lasted entire course while TIMP3 expression was significantly decreased; and 4) a strong correlation between increased dermal matrix expression and induction of regulatory growth factors of VEGF, TGFb, bFGF and CTGF.