Association of Mitochondrial Pyruvate Carrier with the Clinical and Histological Features in Lupus Nephritis

Huanhuan Zhu; Chen Chen; Luhan Geng; Qing Li; Chengning Zhang; Lin Wu; Bo Zhang; Suyan Duan; Changying Xing; Yanggang Yuan

doi:10.2147/IJNRD.S443519

Association of Mitochondrial Pyruvate Carrier with the Clinical and Histological Features in Lupus Nephritis

Int J Nephrol Renovasc Dis. 2024 Jan 19:17:29-38. doi: 10.2147/IJNRD.S443519. eCollection 2024.

Authors

Huanhuan Zhu¹, Chen Chen¹, Luhan Geng¹, Qing Li¹, Chengning Zhang¹, Lin Wu¹, Bo Zhang¹, Suyan Duan^#¹, Changying Xing^#¹, Yanggang Yuan^#¹

Affiliation

¹ Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Background: Mounting evidence suggests that mitochondrial dysfunction contributes to lupus nephritis (LN) pathogenesis. Mitochondrial pyruvate carrier 1 (MPC1) and mitochondrial pyruvate carrier 2 (MPC2) mediating pyruvate transport from the cytoplasm to the mitochondrial matrix, determines the cell survival and cellular energy supply. Here, we aimed to investigate the association of mitochondrial pyruvate carrier expression with the clinical and histological features in LN.

Methods: Patients with biopsy-proven proliferative LN (class III and class IV, n=18) and membranous LN (class V, n=18) were included. Expression of MPC1 and MPC2 were examined by immunohistochemistry. MPC protein levels in the two groups were evaluated by the Student's t-test. Correlation analysis between MPC levels and clinicopathological features was performed by Spearman's rank correlation.

Results: Both MPC1 and MPC2 were exclusively expressed in renal tubules of enrolled LN. Significantly lower MPC1 and MPC2 were observed in patients with proliferative LN compared to membranous LN. In addition, the MPC1 and MPC2 were negatively correlated with SLEDAI-2K score, renal function, and renal pathology activity index.

Conclusion: Both MPC1 and MPC2 were localized in renal tubules, and decreased MPC content was more pronounced in proliferative LN than membranous LN. MPC levels were significantly correlated with renal functions and renal pathology activity.

Keywords: lupus nephritis; membranous; mitochondrial pyruvate carrier; proliferative; tubulointerstitial lesions.

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (82170699, 81870469, 82100767), the Natural Science Foundation of Jiangsu Province (No. BK20191075), the “333 Project” of Jiangsu Province, the Six Talent Peaks Project in Jiangsu Province (WSN-010), “Yiluqihang Shenmingyuanyang” medical development And Scientific Research Fund project on Kidney Diseases (SMYY20220301001), and the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institution. These funding sources were not involved in the design of the study and data collection, analysis, or interpretation. They also played no role in the writing of the manuscript.