Chen Baozhu, Liu Yufeng, Luo Shunchang, Zhou Jialiang, Wang Yijia, He Qiuming, Zhuang Guiying, Hao Hu, Ma Fei, Xiao Xin, Li Sitao
Department of Pediatrics, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510655, China; Biomedical Innovation Center, The Sixth Affiliated Hospital, Sun Yat-sen University, 510655, China.
Center for Medical Research on Innovation and Translation, Guangzhou First People's Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510000, China.
Free Radic Biol Med. 2025 Jan;226:251-265. doi: 10.1016/j.freeradbiomed.2024.11.035. Epub 2024 Nov 19.
Excessive autophagy has been implicated in the pathogenesis of necrotizing enterocolitis (NEC), yet the molecular underpinnings of the autophagy-lysosomal pathway (ALP) in NEC are not well characterized. This study aimed to elucidate alterations within the ALP in NEC by employing RNA sequencing on intestinal tissues obtained from affected infants. Concurrently, we established animal and cellular models of NEC to assess the therapeutic efficacy of itaconic acid (ITA). Our results indicate that the ALP is significantly disrupted in NEC. Notably, ITA was found to modulate the ALP, enhancing autophagic flux and lysosomal function, which consequently alleviated NEC symptoms. Further analysis revealed that ITA's beneficial effects are mediated through the promotion of TFEB nuclear translocation, thereby augmenting the ALP. These findings suggest that targeting the ALP with ITA to modulate TFEB activity may represent a viable therapeutic approach for NEC.
过度自噬与坏死性小肠结肠炎（NEC）的发病机制有关，但NEC中自噬-溶酶体途径（ALP）的分子基础尚未得到充分表征。本研究旨在通过对受影响婴儿的肠道组织进行RNA测序，阐明NEC中ALP的变化。同时，我们建立了NEC的动物和细胞模型，以评估衣康酸（ITA）的治疗效果。我们的结果表明，NEC中ALP明显受损。值得注意的是，发现ITA可调节ALP，增强自噬通量和溶酶体功能，从而缓解NEC症状。进一步分析表明，ITA的有益作用是通过促进TFEB核转位介导的，从而增强了ALP。这些发现表明，用ITA靶向ALP以调节TFEB活性可能是一种可行的NEC治疗方法。
