Growth differentiation factor 11 attenuates sepsis-associated acute kidney injury by reducing inflammation and coagulation via PGC-1α/Nrf2 activation

作者：Hongwei Wang, Minmin Wu, Mian-Mian Zhu, Yiyang Qin, Keqi Wang, Chenyu Wu, Rongrong Zhang, Yin Wang, Chen Zhou, Shuang Luo, Chaosheng Lu, Jingye Pan · 发表于：Cellular & Molecular Biology Letters · 年份：2025 · DOI：10.1186/s11658-025-00762-2 · 被引用次数：6 · 研究领域：TGF-β signaling in diseases、GDF15 and Related Biomarkers、Acute Kidney Injury Research

BACKGROUND: Patients with sepsis commonly endure severe renal dysfunction and damage, hastening to end-stage renal failure with high mortality, and effective treatment options are currently lacking. Growth differentiation factor 11 (GDF11), belonging to the transforming growth factor beta (TGF-β) superfamily, has shown therapeutic potential for numerous acute and chronic inflammatory conditions. Nevertheless, its function in sepsis-associated acute kidney injury (SAKI) remains unclear. PURPOSE: This study sought to explore GDF11's role in SAKI and determine the signaling pathways it modulates. METHODS: Alterations in GDF11 expression in the kidneys of mice with SAKI were analyzed. The influence of GDF11 knockdown and recombinant GDF11 (rGDF11) supplementation on cecal ligation and puncture (CLP)-induced SAKI in mice was determined. RNA sequencing, Western blot, real-time quantitative polymerase chain reaction (RT-qPCR), and kit assays were performed to explore the underlying mechanisms. RESULTS: Tubular epithelial cells and macrophages in the kidneys of CLP-induced SAKI mice exhibited high levels of GDF11 expression. Moreover, gene silencing of GDF11 using adeno-associated virus (AAV) aggravated renal dysfunction, increased tubular damage, and augmented renal apoptosis in CLP-induced SAKI mice. In contrast, replenishment of rGDF11 significantly mitigated these adverse effects. Further studies indicated that GDF11 stimulated the nuclear factor erythroid 2-related factor 2 (Nrf...