Jang Soyoung, Jang Soyeon, Ko Jiwon, Bae Ji-Eun, Hyung Hyejin, Park Ji Yeong, Lim Su-Geun, Park Sijun, Park Song, Yi Junkoo, Kim Seonggon, Kim Myoung Ok, Cho Dong-Hyung, Ryoo Zae Young
School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.
KNU LAMP Research Center, KNU Institute of Basic Sciences, College of Natural Sciences, Kyungpook National University, Daegu, 41566, Republic of Korea.
Sci Rep. 2024 Mar 11;14(1):5908. doi: 10.1038/s41598-024-56216-w.
Inflammatory bowel disease (IBD) is a chronic inflammatory condition that is influenced by various factors, including environmental factors, immune responses, and genetic elements. Among the factors that influence IBD progression, macrophages play a significant role in generating inflammatory mediators, and an increase in the number of activated macrophages contributes to cellular damage, thereby exacerbating the overall inflammatory conditions. HSPA9, a member of the heat shock protein 70 family, plays a crucial role in regulating mitochondrial processes and responding to oxidative stress. HSPA9 deficiency disrupts mitochondrial dynamics, increasing mitochondrial fission and the production of reactive oxygen species. Based on the known functions of HSPA9, we considered the possibility that HSPA9 reduction may contribute to the exacerbation of colitis and investigated its relevance. In a dextran sodium sulfate-induced colitis mouse model, the downregulated HSPA9 exacerbates colitis symptoms, including increased immune cell infiltration, elevated proinflammatory cytokines, decreased tight junctions, and altered macrophage polarization. Moreover, along with the increased mitochondrial fission, we found that the reduction in HSPA9 significantly affected the superoxide dismutase 1 levels and contributed to cellular death. These findings enhance our understanding of the intricate mechanisms underlying colitis and contribute to the development of novel therapeutic approaches for this challenging condition.
炎症性肠病（IBD）是一种慢性炎症性疾病，受多种因素影响，包括环境因素、免疫反应和遗传因素。在影响IBD进展的因素中，巨噬细胞在产生炎症介质方面发挥着重要作用，活化巨噬细胞数量的增加会导致细胞损伤，从而加剧整体炎症状态。热休克蛋白70家族成员HSPA9在调节线粒体过程和应对氧化应激中起关键作用。HSPA9缺乏会破坏线粒体动力学，增加线粒体裂变和活性氧的产生。基于HSPA9的已知功能，我们考虑了HSPA9减少可能导致结肠炎加重的可能性，并对其相关性进行了研究。在葡聚糖硫酸钠诱导的结肠炎小鼠模型中，HSPA9下调会加剧结肠炎症状，包括免疫细胞浸润增加、促炎细胞因子升高、紧密连接减少和巨噬细胞极化改变。此外，随着线粒体裂变增加，我们发现HSPA9的减少显著影响超氧化物歧化酶1水平并导致细胞死亡。这些发现加深了我们对结肠炎潜在复杂机制的理解，并有助于开发针对这种具有挑战性疾病的新型治疗方法。
