2. Academic Validation
  3. The BPIFA2 - LRP5 axis orchestrates mitochondrial dysfunction to mediate kidney injury in lupus nephritis

The BPIFA2 - LRP5 axis orchestrates mitochondrial dysfunction to mediate kidney injury in lupus nephritis

  • Int Immunopharmacol. 2025 Jun 20:162:115114. doi: 10.1016/j.intimp.2025.115114.
Yunhe Liu 1,  Yuexin Tian 1,  Han Wang 1,  Ningning Li 1,  Runqi Zhuo 1,  Huixin Cui 1,  Xinyan Miao 1,  Jinxi Liu 1,  Qingjuan Liu 1,  Wei Zhang 1,  Huifang Guo 2,  Lingling Xing 3,  Lin Yang 3,  Xiaojuan Feng 4,  Shuxia Liu 5
Affiliations

Affiliations

  • 1 Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang 050017, China.
  • 2 Department of Rheumatology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 3 Department of Nephrology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, China.
  • 4 Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang 050017, China.. Electronic address: 18500783@hebmu.edu.cn.
  • 5 Department of Pathology, Center of Metabolic Diseases and Cancer Research, Institute of Medical and Health Science, Hebei Medical University, Key Laboratory of Kidney Diseases of Hebei Province, Shijiazhuang 050017, China.. Electronic address: shuxialiu@hebmu.edu.cn.
PMID: 40543103 DOI: 10.1016/j.intimp.2025.115114
Abstract

Kidney injury, particularly the processes of inflammation and fibrosis, is a critical pathological feature of Lupus nephritis (LN). BPI fold-containing family A member 2 (BPIFA2), a recently identified parotid gland secretory protein, serves as an early biomarker for acute kidney injury (AKI) and has been shown to promote AKI development. However, the role of BPIFA2 in regulating LN remains largely unclear. In this study, we detected significant BPIFA2 expression in renal tubular epithelial cells of LN patients and animal models, which was strongly correlated with the degree of renal injury. Specifically, targeted knockdown of BPIFA2 in renal tubular epithelial cells significantly alleviated renal tubular injury in LN mice, while its overexpression exacerbated the injury. Mechanistically, under LN conditions, we found that BPIFA2 interacted with low density lipoprotein receptor-related protein 5 (LRP5) in HK-2 cells, resulting in mitochondrial dysfunction and ultimately leading to renal tubular injury. Collectively, our findings not only reveal a novel regulatory mechanism of renal tubular injury in LN but also suggest BPIFA2 as a promising therapeutic target for mitigating LN-associated kidney injury.

Keywords

BPIFA2; Kidney injury; LRP5; Lupus nephritis; Mitochondria; Renal tubular epithelial cells.

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