2. Academic Validation
  3. Formyl peptide receptor 2 activation by mitochondrial formyl peptides stimulates the neutrophil proinflammatory response via the ERK pathway and exacerbates ischemia-reperfusion injury

Formyl peptide receptor 2 activation by mitochondrial formyl peptides stimulates the neutrophil proinflammatory response via the ERK pathway and exacerbates ischemia-reperfusion injury

  • Cell Mol Biol Lett. 2023 Jan 19;28(1):4. doi: 10.1186/s11658-023-00416-1.
Yirui Cao # 1 2,  Juntao Chen # 1 2,  Feng Liu # 3,  Guisheng Qi 1,  Yufeng Zhao 1 2,  Shihao Xu 1 2,  Jiyan Wang 1 2,  Tongyu Zhu # 4 5,  Yi Zhang # 6,  Yichen Jia # 7
Affiliations

Affiliations

  • 1 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China.
  • 2 Shanghai Key Laboratory of Organ Transplantation, Shanghai, China.
  • 3 Department of Integrative Medicine, Huashan Hospital Fudan University, Shanghai, People's Republic of China.
  • 4 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • 5 Shanghai Key Laboratory of Organ Transplantation, Shanghai, China. [email protected].
  • 6 Zhongshan Hospital Institute of Clinical Science, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • 7 Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, China. [email protected].
  • # Contributed equally.
PMID: 36658472 DOI: 10.1186/s11658-023-00416-1
Abstract

Background: Ischemia-reperfusion injury (IRI) is an inevitable process in renal transplantation that significantly increases the risk of delayed graft function, acute rejection, and even graft loss. Formyl peptide receptor 2 (FPR2) is an important receptor in multiple septic and aseptic injuries, but its functions in kidney IRI are still unclear. This study was designed to reveal the pathological role of FPR2 in kidney IRI and its functional mechanisms.

Methods: To explore the mechanism of FPR2 in kidney IRI, the model rats were sacrificed after IRI surgery. Immunofluorescence, enzyme-linked immunosorbent assays, and western blotting were used to detect differences in the expression of FPR2 and its ligands between the IRI and control groups. WRW4 (WRWWWW-NH2), a specific antagonist of FPR2, was administered to kidney IRI rats. Kidney function and pathological damage were detected to assess kidney injury and recovery. Flow cytometry was used to quantitatively compare neutrophil infiltration among the experimental groups. Mitochondrial formyl Peptides (mtFPs) were synthesized and administered to primary rat neutrophils together with the specific FPR family antagonist WRW4 to verify our hypothesis in vitro. Western blotting and cell function assays were used to examine the functions and signaling pathways that FPR2 mediates in neutrophils.

Results: FPR2 was activated mainly by mtFPs during the acute phase of IRI, mediating neutrophil migration and Reactive Oxygen Species production in the rat kidney through the ERK1/2 pathway. FPR2 blockade in the early phase protected rat kidneys from IRI.

Conclusions: mtFPs activated FPR2 during the acute phase of IRI and mediated rat kidney injury by activating the migration and Reactive Oxygen Species generation of neutrophils through the ERK1/2 pathway.

Keywords

Formyl peptide receptor 2; Kidney IRI; Migration; Mitochondrial-derived formyl peptides; Neutrophil.

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