School of Basic Medical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
Laboratory Animal Center, Wenzhou Medical University, Wenzhou 325035, China.
Biochim Biophys Acta Mol Basis Dis. 2022 Nov 1;1868(11):166518. doi: 10.1016/j.bbadis.2022.166518. Epub 2022 Aug 10.
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.
皮肤伤口愈合是一个复杂的过程，其特征是初始炎症期后紧接着是增生期。NLRC3 在先天免疫、炎症调节和肿瘤细胞生长中发挥重要作用。然而，NLRC3 在伤口愈合中的功能尚不清楚。在这里，我们使用 Nlrc3 基因敲除 (Nlrc3) 小鼠研究了 NLRC3 在急性皮肤伤口愈合中的功能。我们的结果表明，与野生型 (WT) 小鼠相比，Nlrc3 小鼠的皮肤伤口修复明显加快。NLRC3 缺乏促进了伤口中的炎症和增生期，增强了炎症反应，增加了再上皮化和肉芽组织形成，这些表型主要归因于对 p53 信号的调节作用。在机制上，我们揭示了 NLRC3 和 p53 信号之间的新的串扰，并发现 NLRC3 可以通过 HSP90 依赖性方式介导 p53 的泛素化和降解。总之，我们的研究表明，NLRC3 是伤口愈合过程中炎症反应和细胞增殖的关键负调节剂，阻断 NLRC3 可能代表一种加速伤口愈合的潜在方法。
