Liu Yangdan, Ho Chiakang, Wen Dongsheng, Sun Jiaming, Liu Yuxin, Li Qingfeng, Zhang Yifan, Gao Ya
JCI Insight. 2025 Jan 21;10(4):e184457. doi: 10.1172/jci.insight.184457.
Chronic wounds have emerged as a tough clinical challenge. An improved understanding of wound-healing mechanisms is paramount. Collagen XVII (COL17), a pivotal constituent of hemidesmosomes, holds considerable promise for regulating epidermal cell adhesion to the basement membrane as well as for epidermal cell motility and self-renewal of epidermal stem cells. However, the precise role of COL17 in wound repair remains elusive, and the upstream regulatory mechanisms involved have not been fully elucidated. In this study, we delineated the temporal and spatial expression patterns of COL17 at the epidermal wound edge. Subsequently, we investigated the indispensable role of COL17 in keratinocyte activation and reepithelialization during wound healing, demonstrating the restoration of the normal repair process by COL17 overexpression in diabetic wounds. Notably, we identified a key transcriptional signaling pathway for COL17, wherein pyruvate kinase isozyme M2 (PKM2) promotes phosphorylation of STAT3, leading to its activation and subsequent induction of COL17 expression upon injury. Ultimately, by manipulating this pathway using the PKM2 nuclear translocator SAICAR, we revealed a promising therapeutic strategy for enhancing the healing of chronic wounds.
慢性伤口已成为一项严峻的临床挑战。更好地理解伤口愈合机制至关重要。胶原蛋白 XVII（COL17）是半桥粒的关键组成部分，在调节表皮细胞与基底膜的黏附以及表皮细胞运动和表皮干细胞自我更新方面具有巨大潜力。然而，COL17 在伤口修复中的精确作用仍不清楚，其涉及的上游调控机制也尚未完全阐明。在本研究中，我们描绘了 COL17 在表皮伤口边缘的时空表达模式。随后，我们研究了 COL17 在伤口愈合过程中角质形成细胞活化和再上皮化中的不可或缺作用，证明了通过在糖尿病伤口中过表达 COL17 可恢复正常修复过程。值得注意的是，我们确定了 COL17 的一个关键转录信号通路，其中丙酮酸激酶同工酶 M2（PKM2）促进 STAT3 的磷酸化，导致其激活并随后在损伤时诱导 COL17 表达。最终，通过使用 PKM2 核转运体 SAICAR 操纵该通路，我们揭示了一种增强慢性伤口愈合的有前景的治疗策略。
