2. Academic Validation
  3. Mertk-driven tunneling nanotube formation in macrophages preserves mitochondrial homeostasis during kidney Ischemia-Reperfusion Attack

Mertk-driven tunneling nanotube formation in macrophages preserves mitochondrial homeostasis during kidney Ischemia-Reperfusion Attack

  • Biochem Pharmacol. 2026 Apr:246:117713. doi: 10.1016/j.bcp.2026.117713.
Jun Zeng 1,  Ruoqing Li 2,  Liyin Chai 1,  Ying Zhang 1,  Li Gong 1,  Xiaolin Yuan 1,  Qiufang Bai 3,  Shuping Xiao 3,  Jialian Wang 4,  Sha Xiang 1,  Haili Sun 1,  Zhengyang Liu 1,  Xingqing Chen 1,  Ning Li 1,  Bailin Niu 5,  Mei Mei 6,  Bingbing Shen 7
Affiliations

Affiliations

  • 1 Department of Nephrology, Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.
  • 2 Department of General Practice, Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.
  • 3 Department of Nephrology and Rheumatology, The First People's Hospital of Chongqing High-tech Industrial Development Zone, Chongqing, China.
  • 4 Department of Intensive Care Medicine, Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China.
  • 5 Department of Intensive Care Medicine, Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China. Electronic address: [email protected].
  • 6 Department of Nephrology and Rheumatology, Chongqing Key Laboratory of Emergency Medicine, Shapingba Hospital Affiliated to Chongqing University, School of Medicine, Chongqing University, Chongqing, China. Electronic address: [email protected].
  • 7 Department of Nephrology, Chongqing Key Laboratory of Emergency Medicine, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, China; Department of Nephrology and Rheumatology, The First People's Hospital of Chongqing High-tech Industrial Development Zone, Chongqing, China. Electronic address: [email protected].
PMID: 41544856 DOI: 10.1016/j.bcp.2026.117713
Abstract

Renal ischemia-reperfusion (I/R) injury is a critical pathological process in organ transplantation and acute kidney injury (AKI), involving oxidative stress, inflammation, and mitochondrial dysfunction. Macrophage-expressed Mertk, a key regulator of tissue homeostasis, remains understudied in renal I/R injury. Mertk knockout (Mertk-KO) mice and their wild-type (WT) littermates were subjected to renal I/R injury. Mertk deficiency exacerbated renal tubular injury, inflammation, and oxidative stress in I/R-induced AKI. ATP production decreased, and mitochondrial morphology was disrupted in RTECs from Mertk-KO mice compared to WT mice. In vitro studies demonstrated that knockdown of Mertk in kidney-resident macrophages (KRMs) aggravated renal tubular epithelial cells (RTECs) injury, proliferation inhibition, Apoptosis, and mitochondrial dysfunction under hypoxia-reoxygenation (H/R) conditions. Conversely, Mertk overexpression in KRMs attenuated these detrimental effects. Notably, Mertk overexpression facilitated tunneling nanotubes (TNTs) formation and promoted intercellular mitochondrial trafficking between KRMs and RTECs, maintaining mitochondrial homeostasis in RTECs. LAT-A treatment inhibited TNTs formation and abrogated the protective effects of Mertk overexpression. This study established Mertk as a critical mediator of KRMs-RTECs crosstalk through TNTs-dependent mitochondrial homeostasis regulation, providing mechanistic insights into AKI progression. Mertk-expressed KRMs-mediated mitochondrial transfer through TNT formation, providing a potential therapeutic target for AKI.

Keywords

Acute kidney injury; Ischemia–reperfusion; Kidney-resident macrophages; Mertk; Mitochondrial homeostasis; Tunneling nanotubes.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-E70005A
    Zinc peptidase, Matrix metalloproteinases (MMPs)
    MMP