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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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Autores principales: Fan, Zuyan, Gao, Yan, Jiang, Nan, Zhang, Fengxia, Liu, Shuangxin, Li, Quhuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592916/
https://www.ncbi.nlm.nih.gov/pubmed/36304455
http://dx.doi.org/10.3389/fimmu.2022.979995
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author Fan, Zuyan
Gao, Yan
Jiang, Nan
Zhang, Fengxia
Liu, Shuangxin
Li, Quhuan
author_facet Fan, Zuyan
Gao, Yan
Jiang, Nan
Zhang, Fengxia
Liu, Shuangxin
Li, Quhuan
author_sort Fan, Zuyan
collection PubMed
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.
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spelling pubmed-95929162022-10-26 Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury Fan, Zuyan Gao, Yan Jiang, Nan Zhang, Fengxia Liu, Shuangxin Li, Quhuan Front Immunol Immunology 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. Frontiers Media S.A. 2022-10-11 /pmc/articles/PMC9592916/ /pubmed/36304455 http://dx.doi.org/10.3389/fimmu.2022.979995 Text en Copyright © 2022 Fan, Gao, Jiang, Zhang, Liu and Li https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Fan, Zuyan
Gao, Yan
Jiang, Nan
Zhang, Fengxia
Liu, Shuangxin
Li, Quhuan
Immune-related SERPINA3 as a biomarker involved in diabetic nephropathy renal tubular injury
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 Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9592916/
https://www.ncbi.nlm.nih.gov/pubmed/36304455
http://dx.doi.org/10.3389/fimmu.2022.979995
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