NLRC3 deficiency promotes cutaneous wound healing due to the inhibition of p53 signaling

Cutaneous wound healing is a complicated process that is characterized by an initial inflammatory phase followed by a proliferative phase. NLRC3 plays important roles in innate immunity, inflammatory regulation and tumor cell growth. However, the function of NLRC3 in wound healing remains unclear. Here, we investigated the function of NLRC3 in acute cutaneous wound healing using Nlrc3 gene knockout (Nlrc3−/−) mice. Our results demonstrated that skin wound repair in Nlrc3−/− mice was significantly accelerated compared with that in wild-type (WT) mice. NLRC3 deficiency promoted the inflammatory and proliferative phases in wounds enhanced the inflammatory response and increased re-epithelialization and granulation tissue formation, and these phenotypes were primarily ascribed to regulatory effects on p53 signaling. Mechanistically, we uncovered novel crosstalk between NLRC3 and p53 signaling and revealed that NLRC3 could mediate the ubiquitination and degradation of p53 in an Hsp90-dependent manner. In conclusion, our study suggests that NLRC3 is a critical negative regulator of the inflammatory response and cell proliferation during wound healing and that blocking NLRC3 may represent a potential approach for accelerating wound healing. [Display omitted] •The role of NLRC3 in skin wound healing was investigated.•NLRC3 deficiency accelerates skin wound healing in mice by promoting inflammation and the proliferation phase.•NLRC3 increases the stability of p53 in wounds by preventing its ubiquitination and degradation.•The interaction between NLRC3 and the chaperone protein Hsp90 prevents Hsp90/MDM2-mediated degradation of p53.