School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, China.
Department of Pharmacy, Zhejiang Provincial People's Hospital (Affiliated People's Hospital, Hangzhou Medical College), Hangzhou, China.
FASEB J. 2024 Oct 15;38(19):e70092. doi: 10.1096/fj.202401238R.
Acute kidney injury (AKI) is a devastating clinical condition characterized by an abrupt loss of renal function. The pathophysiology of AKI involves diverse processes and elements, of which survival and regeneration have been established to be significant hallmarks. And early studies have confirmed the fundamental role of FGFs in the regulation of AKI pathology, although the association between FGF18 and AKI still remains elusive. Our study demonstrates a substantial up-regulation of FGF18 in the renal tubules of mice subjected to ischemia. Notably, targeted overexpression of FGF18 effectively mitigates the impairment of kidney function induced by AKI. Mechanistically, FGF18 facilitates cell proliferation and anti-apoptosis in RTECs by enhancing the expression of YAP and facilitating its translocation to the nucleus. Aside from that, we also discovered that the substantial expression of FGF18 under ischemic conditions is HIF-1α dependent. This study aims to uncover the inherent mechanism behind the beneficial effects of FGF18 in attenuating AKI. By doing so, it aims to offer novel insights into the development of therapeutic strategies for AKI.
急性肾损伤（AKI）是一种破坏性的临床病症，其特征是肾功能突然丧失。AKI 的病理生理学涉及多种过程和因素，其中生存和再生已被确定为重要的标志。早期研究已经证实了 FGFs 在调节 AKI 病理中的基本作用，尽管 FGF18 与 AKI 之间的关联仍然难以捉摸。我们的研究表明，在缺血小鼠的肾小管中 FGF18 大量上调。值得注意的是，FGF18 的靶向过表达可有效减轻 AKI 引起的肾功能损害。从机制上讲，FGF18 通过增强 YAP 的表达并促进其向核内易位，促进 RTECs 的细胞增殖和抗细胞凋亡。除此之外，我们还发现，在缺血条件下大量表达的 FGF18 依赖于 HIF-1α。本研究旨在揭示 FGF18 减轻 AKI 的有益作用背后的内在机制。通过这样做，它旨在为 AKI 的治疗策略的发展提供新的见解。
