Abstract: SA-PO0257
Fibroblast-Derived Fstl1 Protects Against Tubular Cell Damage in AKI via the DIP2a-Bach1-HGF Axis
Session Information
- AKI: Mechanisms - Cell Signaling
October 24, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Kong, Yonglun, Shenzhen Research Institute, ShenZhen, GuangDong, China
- Wang, Yang, Shenzhen Research Institute, ShenZhen, GuangDong, China
- Zhang, Yu, Harbin Medical University, Harbin, Heilongjiang, China
- Xia, Yin, Shenzhen Research Institute, ShenZhen, GuangDong, China
Background
In acute kidney injury (AKI) induced by ischemia, nephrotoxins, or surgical procedures, renal tubular cells are the primary cell type damaged. Other cell types, such as macrophages, monocytes and T cells, are also critically involved in the pathogenesis of AKI. However, the role of fibroblasts during AKI remains largely unknown. Fstl1 is a secreted protein previously implicated in renal fibrosis. The function of fibroblast-derived Fstl1 has not been studied in AKI.
Methods
We measured serum and urinary Fstl1 protein levels in non-AKI and AKI patients. AKI mouse models (ischemia-reperfusion and cisplatin injection) were established in Pdgfr-β+ cell–specific Fstl1 knockout (Fstl1 fKO) mice. Cell–cell communication intensity in wild-type (WT) and Fstl1 fKO mice after ischemia-reperfusion (IR) was analyzed by single-cell RNA sequencing. Co-immunoprecipitation, TUNEL, nuclear protein extraction, and luciferase assays were employed to elucidate the mechanism by which fibroblast-derived Fstl1 mediates tubular cell apoptosis in AKI.
Results
Serum and urinary Fstl1 protein levels were significantly elevated in AKI patients, and they were negatively correlated with serum creatinine, BUN, and CRP levels. Fibroblast-specific Fstl1 deficiency worsened renal function in mice subjected to IR- or cisplatin-induced AKI. Moreover, tubular injury markers (Kim1 and Ngal) and inflammatory markers (IL-6, IL-1β, and Adgre1) were upregulated in Fstl1 fKO mice compared with WT mice. Mechanistically, Fstl1 signaled through the DIP2a receptor to promote SRC Y416 phosphorylation, which then stimulated Bach1 phosphorylation at Y483, followed by its nuclear export, thereby upregulating Hgf expression in fibroblasts. HGF released from fibroblasts acted through the c-Met receptor in renal tubular cells to reduce cell apoptosis in injured kidneys.
Conclusion
Fibroblast-derived Fstl1 protects against renal tubular cell apoptosis by upregulating HGF secretion from fibroblasts via the DIP2a-SRC-Bach1 cascade.