Recombinant human collagen XVII protects skin basement membrane integrity by inhibiting the MAPK and Wnt signaling pathways

Abstract

Collagen XVII is a key component linking the cyto‑ skeleton to the basement membrane, serving an essential role in maintaining skin integrity. With the advancement of synthetic biology, recombinant human collagen XVII (RHCXVII) has emerged as a promising novel collagen material. The present study aimed to elucidate the efficacy and mechanisms of action of RHCXVII in protecting skin basement membrane integrity. A skin injury model was established using ultraviolet B (UVB) irradiation on human HaCaT keratinocytes treated with RHCXVII. The effects of RHCXVII on cell migration and adhesion were assessed using wound healing assay and hematoxylin and eosin staining, respectively. The expression of key extracellular matrix (ECM) components such as collagen IV, collagen VII, laminin 332 and integrin α6 (ITGA6) were quantified using reverse transcription‑quantitative PCR and western blotting. The mechanism of action of RHCXVII in protecting skin basement membrane integrity was investi‑ gated using a phosphorylated‑antibody array and verified by western blotting. RHCXVII significantly increased the migra‑ tion and adhesion of UVB‑irradiated HaCaT cells (P<0.01). Additionally, RHCXVII significantly upregulated expression levels of collagen type IV α1 chain, collagen type VII α1 chain, laminin subunit β3 and ITGA6 in UVB‑irradiated HaCaT cells (P<0.05). RHCXVII significantly inhibited the phosphoryla‑ tion of p38 and c‑Jun in the MAPK and Wnt signaling pathways (P<0.01). In conclusion, RHCXVII protected skin basement membrane integrity by enhancing migration and adhesion of keratinocytes, upregulating key ECM components and inhibiting protein phosphorylation in MAPK and Wnt path‑ ways. The present study enhanced the current understanding of RHCXVII as a protector of skin basement membrane integrity. Furthermore, the present study highlighted clinical implications and the broad therapeutic potential of RHCXVII in both medical and cosmetic application.