Qijiao Wei,1 Xinchen Wu,2 Zhihan Chen,3 He Lin,3 Lei Xiong,2 Na Wang4 

1Department of Rheumatology, Children’s Hospital of Fudan University, Shanghai, 201102, People’s Republic of China; 2The First School of Clinical Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, 650500, People’s Republic of China; 3Department of Rheumatology, Fujian Provincial Hospital, Fuzhou, 355000, People’s Republic of China; 4Department of Traditional Chinese Medicine, Children’s Hospital of Fudan University, Shanghai, 201102, People’s Republic of China

Correspondence: Na Wang, Children’s Hospital of Fudan University, No. 399 Wanyuan, Shanghai, People’s Republic of China, Email 18203638814@163.com Lei Xiong, The First School of Clinical Medicine, Yunnan University of Chinese Medicine, No. 1 huachen, Xishan District, Kunming, Yunnan Province, People’s Republic of China, Email xlluck@sina.com

Background: The glomerular injury is associated with different pathogeneses, and podocyte damage is common in various ISN/RPS class lupus nephritis (LN). In podocyte, mitochondrial morphological changes are observed in lupus nephritis (LN) in our previous study. This study aimed to explore mitochondrial fission proteins expression in podocytes using bioinformatics analysis and further to investigate the associations between mitochondrial fission proteins and laboratory features in LN.
Methods: To determine the differentially expressed genes (DEGs) between LN and normal controls, we downloaded and analyzed microarray datasets. Then download the mitochondrial genes list from the MitoMiner 4.0 database, then take the genes that are common with the DEGs. Functional enrichment analyses were then performed. Then mitochondrial fission was observed through electron microscope. We performed immunofluorescence staining to explore the expression of mitochondrial fission proteins in LN patients.
Results: Among these 658 DEGs, 5 DEGs related to mitochondrial dynamics were identified. Mitochondrial dynamics proteins were involved in mitophagy. Mitochondrial fission proteins Drp1 and Fis1 staining were significantly enhanced compared to that in the controls. 24h-UTP are positively correlated with mitochondrial fission proteins expression.
Conclusion: Mitochondrial fission was observed in LN patients’ podocytes. Mitochondrial fission proteins Drp1 and Fis1 were overproduced in podocytes, and then they can lead to mitochondrial fission, which may aggravate podocyte damage and proteinuria. While the mechanism still needs to be explored.

Keywords: lupus nephritis, podocyte injury, mitochondria fission, Drp1, Fis1