Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis
The molecular mechanisms underlying lupus nephritis (LN) pathogenesis are not fully understood. Hydrogen sulfide (H2S) is involved in many pathological and physiological processes. We sought to investigate the roles of H2S in LN pathogenesis. H2S synthase cystathionine–lyase (CSE) and cystathionine–...
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MDPI AG
2023-02-01
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| Series: | Biology |
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| Online Access: | https://www.mdpi.com/2079-7737/12/2/318 |
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| author | Xuan Wang Tao Lin Yifei He Yueyuan Zhou Yi Peng Weiru Zhang Xin Ni |
| author_facet | Xuan Wang Tao Lin Yifei He Yueyuan Zhou Yi Peng Weiru Zhang Xin Ni |
| author_sort | Xuan Wang |
| collection | DOAJ |
| description | The molecular mechanisms underlying lupus nephritis (LN) pathogenesis are not fully understood. Hydrogen sulfide (H2S) is involved in many pathological and physiological processes. We sought to investigate the roles of H2S in LN pathogenesis. H2S synthase cystathionine–lyase (CSE) and cystathionine–synthetase (CBS) expression was downregulated in renal tissues of patients with LN and their levels were associated with LN’s prognosis using the Nephroseq database. Reduced CSE and CBS protein expression in kidney tissues of LN patients and MRL/lpr mice were confirmed by immunohistochemistry. CSE and CBS mRNA levels were reduced in MRL/lpr and pristine- and R848-induced lupus mice. Given that H2S exerts an anti-inflammatory role partly via regulating inflammatory transcription factors (TFs), we analyzed hub TFs by using a bioinformatics approach. It showed that STAT1, RELA, and T-cell-related signaling pathways were enriched in LN. Increased STAT1 and RELA expression were confirmed in renal tissues of LN patients. Treatment of MRL/lpr and pristine mice with H2S donors alleviated systemic lupus erythematosus (SLE) phenotypes and renal injury. H2S donors inhibited RELA level and T-cell infiltration in the kidneys of MRL/lpr and pristine mice. Our data indicated that CSE/CBS/H2S contributes to LN pathogenesis. Supplementation of H2S would be a potential therapeutic strategy for LN. |
| first_indexed | 2024-03-11T09:08:21Z |
| format | Article |
| id | doaj.art-c55982f7e03a4992b3c5a1f8fb6b30be |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T09:08:21Z |
| publishDate | 2023-02-01 |
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| spelling | doaj.art-c55982f7e03a4992b3c5a1f8fb6b30be2023-11-16T19:14:47ZengMDPI AGBiology2079-77372023-02-0112231810.3390/biology12020318Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus NephritisXuan Wang0Tao Lin1Yifei He2Yueyuan Zhou3Yi Peng4Weiru Zhang5Xin Ni6Department of General Medicine, Xiangya Hospital, Central South University, Changsha 410008, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, ChinaNational Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, ChinaDepartment of General Medicine, Xiangya Hospital, Central South University, Changsha 410008, ChinaInternational Collaborative Research Center for Medical Metabolomics, Xiangya Hospital, Central South University, Changsha 410008, ChinaThe molecular mechanisms underlying lupus nephritis (LN) pathogenesis are not fully understood. Hydrogen sulfide (H2S) is involved in many pathological and physiological processes. We sought to investigate the roles of H2S in LN pathogenesis. H2S synthase cystathionine–lyase (CSE) and cystathionine–synthetase (CBS) expression was downregulated in renal tissues of patients with LN and their levels were associated with LN’s prognosis using the Nephroseq database. Reduced CSE and CBS protein expression in kidney tissues of LN patients and MRL/lpr mice were confirmed by immunohistochemistry. CSE and CBS mRNA levels were reduced in MRL/lpr and pristine- and R848-induced lupus mice. Given that H2S exerts an anti-inflammatory role partly via regulating inflammatory transcription factors (TFs), we analyzed hub TFs by using a bioinformatics approach. It showed that STAT1, RELA, and T-cell-related signaling pathways were enriched in LN. Increased STAT1 and RELA expression were confirmed in renal tissues of LN patients. Treatment of MRL/lpr and pristine mice with H2S donors alleviated systemic lupus erythematosus (SLE) phenotypes and renal injury. H2S donors inhibited RELA level and T-cell infiltration in the kidneys of MRL/lpr and pristine mice. Our data indicated that CSE/CBS/H2S contributes to LN pathogenesis. Supplementation of H2S would be a potential therapeutic strategy for LN.https://www.mdpi.com/2079-7737/12/2/318H2SCSECBSlupus nephritisSTAT1RELA |
| spellingShingle | Xuan Wang Tao Lin Yifei He Yueyuan Zhou Yi Peng Weiru Zhang Xin Ni Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis Biology H2S CSE CBS lupus nephritis STAT1 RELA |
| title | Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis |
| title_full | Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis |
| title_fullStr | Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis |
| title_full_unstemmed | Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis |
| title_short | Reduced Renal CSE/CBS/H2S Contributes to the Progress of Lupus Nephritis |
| title_sort | reduced renal cse cbs h2s contributes to the progress of lupus nephritis |
| topic | H2S CSE CBS lupus nephritis STAT1 RELA |
| url | https://www.mdpi.com/2079-7737/12/2/318 |
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