Department of Plastic and Reconstructive Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430000, China.
Biomolecules. 2022 Mar 7;12(3):410. doi: 10.3390/biom12030410.
Acute lung injury is the most common type of organ damage with high incidence and mortality in sepsis, which is a poorly understood syndrome of disordered inflammation. The aims of this study are to explore whether heat shock protein 70 (HSP70), as a molecular chaperone, attenuates the septic lung injury, and to understand the underlying mechanisms. In our study, treatment with HSP70 ameliorated the survival rate, dysfunction of lung, inflammation, and apoptosis in cecal ligation and puncture (CLP)-treated mice as well as in LPS-treated human alveolar epithelial cells. Furthermore, HSP70 interacted with KANK2, leading to reversed cell viability and reduced apoptosis-inducing factor (AIF) and apoptosis. Additionally, knockdown of KANK2 in epithelial cells and deletion of gene in CLP mice aggravated apoptosis and tissue damage, suggesting that interaction of KANK2 and HSP70 is critical for protecting lung injury induced by sepsis. HSP70 plays an important role in protection of acute lung injury caused by sepsis through interaction with KANK2 to reduce AIF release and apoptotic cell. HSP70 is a novel potential therapeutic approach for attenuation of septic lung injury.
急性肺损伤是脓毒症中最常见的器官损伤类型，发病率和死亡率都很高，而脓毒症是一种炎症失调的综合征，其发病机制尚未完全阐明。本研究旨在探讨热休克蛋白 70（HSP70）作为分子伴侣是否能减轻脓毒症性肺损伤，并探讨其潜在机制。在本研究中，HSP70 的治疗改善了盲肠结扎和穿刺（CLP）处理的小鼠以及脂多糖处理的人肺泡上皮细胞中的存活率、肺功能障碍、炎症和细胞凋亡。此外，HSP70 与 KANK2 相互作用，导致细胞活力恢复，凋亡诱导因子（AIF）和凋亡减少。此外，上皮细胞中 KANK2 的敲低和 CLP 小鼠中基因的缺失加重了细胞凋亡和组织损伤，表明 KANK2 和 HSP70 的相互作用对于保护脓毒症引起的肺损伤至关重要。HSP70 通过与 KANK2 相互作用减少 AIF 的释放和凋亡细胞，在保护脓毒症引起的急性肺损伤方面发挥重要作用。HSP70 是减轻脓毒症性肺损伤的一种新的潜在治疗方法。
