Comparative proteomic analysis of children FSGS FFPE tissues

Jiajia Ni; Sha Tian; Lin Bai; Qianying Lv; Jialu Liu; Jiaojiao Liu; Ye Fang; Yihui Zhai; Qian Shen; Jia Rao; Chen Ding; Hong Xu

doi:10.1186/s12887-022-03764-7

BMC Pediatrics (Dec 2022)

Comparative proteomic analysis of children FSGS FFPE tissues

Jiajia Ni,
Sha Tian,
Lin Bai,
Qianying Lv,
Jialu Liu,
Jiaojiao Liu,
Ye Fang,
Yihui Zhai,
Qian Shen,
Jia Rao,
Chen Ding,
Hong Xu

Affiliations

Jiajia Ni: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Sha Tian: State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University
Lin Bai: State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University
Qianying Lv: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Jialu Liu: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Jiaojiao Liu: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Ye Fang: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Yihui Zhai: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Qian Shen: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Jia Rao: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China
Chen Ding: State Key Laboratory of Genetic Engineering and Collaborative Innovation Center for Genetics and Development, School of Life Sciences, Institute of Biomedical Sciences, Human Phenome Institute, Zhongshan Hospital, Fudan University
Hong Xu: Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of China

DOI: https://doi.org/10.1186/s12887-022-03764-7
Journal volume & issue: Vol. 22, no. 1
pp. 1 – 9

Abstract

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Abstract Background In children, focal segmental glomerulosclerosis (FSGS) is the main cause of steroid resistant nephrotic syndrome (SRNS). To identify specific candidates and the mechanism of steroid resistance, we examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods Renal biopsies from seven steroid-sensitive (SS) and eleven steroid-resistant (SR) children FSGS patients were obtained. We examined the formalin-fixed paraffin embedded (FFPE) renal tissue protein profiles via liquid chromatography tandem mass spectrometry (LC-MS/MS). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and Gene Ontology (GO) analysis, as well as the construction of protein-protein interaction (PPI) network were performed. Two proteins were further valiadated by immunohistochemistry staining in FSGS patients and mice models. Results In total, we quantified more than 4000 proteins, of which 325 were found to be differentially expressed proteins (DEPs) between the SS and SR group (foldchange ≥2, P<0.05). The results of GO revealed that the most significant up-regulated proteins were primarily related to protein transportation, regulation of the complement activation process and cytolysis. Moreover, clustering analysis showed differences in the pathways (lysosome, terminal pathway of complement) between the two groups. Among these potential candidates, validation analyses for LAMP1 and ACSL4 were conducted. LAMP1 was observed to have a higher expression in glomerulus, while ACSL4 was expressed more in tubular epithelial cells. Conclusions In this study, the potential mechanism and candidates related to steroid resistance in children FSGS patients were identified. It could be helpful in identifying potential therapeutic targets and predicting outcomes with these proteomic changes for children FSGS patients.

Published in BMC Pediatrics

ISSN: 1471-2431 (Online)
Publisher: BMC
Country of publisher: United Kingdom
LCC subjects: Medicine: Pediatrics
Website: https://bmcpediatr.biomedcentral.com

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