Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and has become a serious medical issue globally. Although it is known to be associated with glomerular injury, tubular injury has been found to participate in DN in recent years. However, mechanisms of diabetic renal tubular i...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.979995/full |
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| author | Zuyan Fan Zuyan Fan Yan Gao Yan Gao Nan Jiang Nan Jiang Fengxia Zhang Shuangxin Liu Shuangxin Liu Quhuan Li Quhuan Li |
| author_facet | Zuyan Fan Zuyan Fan Yan Gao Yan Gao Nan Jiang Nan Jiang Fengxia Zhang Shuangxin Liu Shuangxin Liu Quhuan Li Quhuan Li |
| author_sort | Zuyan Fan |
| collection | DOAJ |
| description | Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and has become a serious medical issue globally. Although it is known to be associated with glomerular injury, tubular injury has been found to participate in DN in recent years. However, mechanisms of diabetic renal tubular injury remain unclear. Here, we investigated the differentially expressed genes in the renal tubules of patients with DN by analyzing three RNA-seq datasets downloaded from the Gene Expression Omnibus database. Gene set enrichment analysis and weighted gene co-expression network analysis showed that DN is highly correlated with the immune system. The immune-related gene SERPINA3 was screened out with lasso regression and Kaplan–Meier survival analyses. Considering that SERPINA3 is an inhibitor of mast cell chymase, we examined the expression level of SERPINA3 and chymase in human renal tubular biopsies and found that SERPINA3 was upregulated in DN tubules, which is consistent with the results of the differential expression analysis. Besides, the infiltration and degranulation rates of mast cells are augmented in DN. By summarizing the biological function of SERPINA3, chymase, and mast cells in DN based on our results and those of previous studies, we speculated that SERPINA3 is a protective immune-related molecule that prevents renal tubular injury by inhibiting the proliferation and activation of mast cells and downregulating the activity of chymase. |
| first_indexed | 2024-04-12T13:45:39Z |
| format | Article |
| id | doaj.art-46a5736bea6b442d9bf5d06da790f9cd |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-12T13:45:39Z |
| publishDate | 2022-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-46a5736bea6b442d9bf5d06da790f9cd2022-12-22T03:30:42ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-10-011310.3389/fimmu.2022.979995979995Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injuryZuyan Fan0Zuyan Fan1Yan Gao2Yan Gao3Nan Jiang4Nan Jiang5Fengxia Zhang6Shuangxin Liu7Shuangxin Liu8Quhuan Li9Quhuan Li10School of Bioscience and Bioengineering, South China University of Technology, Guangzhou, ChinaGuangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, ChinaGuangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, ChinaDepartment of Nephrology, School of Medicine, South China University of Technology, Guangzhou, ChinaDepartment of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Nephrology, First Affiliated Hospital of Gannan Medical University, Ganzhou, ChinaDepartment of Nephrology, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaThe Second School of Clinical Medicine, Southern Medical University, Guangzhou, ChinaSchool of Bioscience and Bioengineering, South China University of Technology, Guangzhou, ChinaGuangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, South China University of Technology, Guangzhou, ChinaDiabetic nephropathy (DN) is the leading cause of end-stage renal disease and has become a serious medical issue globally. Although it is known to be associated with glomerular injury, tubular injury has been found to participate in DN in recent years. However, mechanisms of diabetic renal tubular injury remain unclear. Here, we investigated the differentially expressed genes in the renal tubules of patients with DN by analyzing three RNA-seq datasets downloaded from the Gene Expression Omnibus database. Gene set enrichment analysis and weighted gene co-expression network analysis showed that DN is highly correlated with the immune system. The immune-related gene SERPINA3 was screened out with lasso regression and Kaplan–Meier survival analyses. Considering that SERPINA3 is an inhibitor of mast cell chymase, we examined the expression level of SERPINA3 and chymase in human renal tubular biopsies and found that SERPINA3 was upregulated in DN tubules, which is consistent with the results of the differential expression analysis. Besides, the infiltration and degranulation rates of mast cells are augmented in DN. By summarizing the biological function of SERPINA3, chymase, and mast cells in DN based on our results and those of previous studies, we speculated that SERPINA3 is a protective immune-related molecule that prevents renal tubular injury by inhibiting the proliferation and activation of mast cells and downregulating the activity of chymase.https://www.frontiersin.org/articles/10.3389/fimmu.2022.979995/fulldiabetic nephropathyrenal tubulesRNA-SeqbioinformaticSERPINA3 |
| spellingShingle | Zuyan Fan Zuyan Fan Yan Gao Yan Gao Nan Jiang Nan Jiang Fengxia Zhang Shuangxin Liu Shuangxin Liu Quhuan Li Quhuan Li Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury Frontiers in Immunology diabetic nephropathy renal tubules RNA-Seq bioinformatic SERPINA3 |
| title | Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| title_full | Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| title_fullStr | Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| title_full_unstemmed | Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| title_short | Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| title_sort | immune related serpina3 as a biomarker involved in diabetic nephropathy renal tubular injury |
| topic | diabetic nephropathy renal tubules RNA-Seq bioinformatic SERPINA3 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.979995/full |
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