Comparative proteomic analysis of children FSGS FFPE tissues
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...
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | BMC Pediatrics |
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| Online Access: | https://doi.org/10.1186/s12887-022-03764-7 |
| _version_ | 1811196650205478912 |
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| author | Jiajia Ni Sha Tian Lin Bai Qianying Lv Jialu Liu Jiaojiao Liu Ye Fang Yihui Zhai Qian Shen Jia Rao Chen Ding Hong Xu |
| author_facet | Jiajia Ni Sha Tian Lin Bai Qianying Lv Jialu Liu Jiaojiao Liu Ye Fang Yihui Zhai Qian Shen Jia Rao Chen Ding Hong Xu |
| author_sort | Jiajia Ni |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T01:02:32Z |
| format | Article |
| id | doaj.art-a422fc634edc435c9f6394200e8e7e58 |
| institution | Directory Open Access Journal |
| issn | 1471-2431 |
| language | English |
| last_indexed | 2024-04-12T01:02:32Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Pediatrics |
| spelling | doaj.art-a422fc634edc435c9f6394200e8e7e582022-12-22T03:54:25ZengBMCBMC Pediatrics1471-24312022-12-012211910.1186/s12887-022-03764-7Comparative proteomic analysis of children FSGS FFPE tissuesJiajia Ni0Sha Tian1Lin Bai2Qianying Lv3Jialu Liu4Jiaojiao Liu5Ye Fang6Yihui Zhai7Qian Shen8Jia Rao9Chen Ding10Hong Xu11Department of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaState 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 UniversityState 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 UniversityDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaState 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 UniversityDepartment of Nephrology, Children’s Hospital of Fudan University, National Pediatric Medical Center of ChinaAbstract 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.https://doi.org/10.1186/s12887-022-03764-7Focal segmental glomerulosclerosisSteroid resistanceProteomics |
| spellingShingle | Jiajia Ni Sha Tian Lin Bai Qianying Lv Jialu Liu Jiaojiao Liu Ye Fang Yihui Zhai Qian Shen Jia Rao Chen Ding Hong Xu Comparative proteomic analysis of children FSGS FFPE tissues BMC Pediatrics Focal segmental glomerulosclerosis Steroid resistance Proteomics |
| title | Comparative proteomic analysis of children FSGS FFPE tissues |
| title_full | Comparative proteomic analysis of children FSGS FFPE tissues |
| title_fullStr | Comparative proteomic analysis of children FSGS FFPE tissues |
| title_full_unstemmed | Comparative proteomic analysis of children FSGS FFPE tissues |
| title_short | Comparative proteomic analysis of children FSGS FFPE tissues |
| title_sort | comparative proteomic analysis of children fsgs ffpe tissues |
| topic | Focal segmental glomerulosclerosis Steroid resistance Proteomics |
| url | https://doi.org/10.1186/s12887-022-03764-7 |
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