Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension
BackgroundThere is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SA...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1258646/full |
| _version_ | 1797400565751218176 |
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| author | Xin Zhang Xin Zhang Xiaoqian Deng Liangliang Zhang Pengbo Wang Xia Tong Yan Mo Yuansheng Zhang Yan Zhang Chunheng Mo Chunheng Mo Lanlan Zhang |
| author_facet | Xin Zhang Xin Zhang Xiaoqian Deng Liangliang Zhang Pengbo Wang Xia Tong Yan Mo Yuansheng Zhang Yan Zhang Chunheng Mo Chunheng Mo Lanlan Zhang |
| author_sort | Xin Zhang |
| collection | DOAJ |
| description | BackgroundThere is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SARS-CoV-2 infection.MethodUsing single-cell meta-analysis in combination with bulk-RNA analysis, we identified three drug targets and potential receptors for SARS-CoV-2 infection in lung tissues from patients with diabetes, hypertension, and hypertension-diabetes, referred to as “co-morbid” patients. Using single-cell meta-analysis analysis in combination with bulk-RNA, we identified drug targets and potential receptors for SARS-CoV-2 infection in the three co-morbidities.ResultsThe single-cell meta-analysis of lung samples from SARS-CoV-2-infected individuals with diabetes, hypertension, and hypertension-diabetes comorbidity revealed an upregulation of fibroblast subpopulations in these disease conditions associated with a predictive decrease in lung function. To further investigate the response of fibroblasts to therapeutic targets in hypertension and diabetes, we analyzed 35 upregulated targets in both diabetes and hypertension. Interestingly, among these targets, five specific genes were upregulated in fibroblasts, suggesting their potential association with enhanced activation of endothelial cells. Furthermore, our investigation into the underlying mechanisms driving fibroblast upregulation indicated that KREMEN1, rather than ACE2, could be the receptor responsible for fibroblast activation. This finding adds novel insights into the molecular processes involved in fibroblast modulation in the context of SARS-CoV-2 infection within these comorbid conditions. Lastly, we compared the efficacy of Pirfenidone and Nintedanib as therapeutic interventions targeting fibroblasts prone to pulmonary fibrosis. Our findings suggest that Nintedanib may be a more suitable treatment option for COVID-19 patients with diabetes and hypertension who exhibit fibrotic lung lesions.ConclusionIn the context of SARS-CoV-2 infections, diabetes, hypertension, and their coexistence predominantly lead to myofibroblast proliferation. This phenomenon could be attributed to the upregulation of activated endothelial cells. Moreover, it is noteworthy that therapeutic interventions targeting hypertension-diabetes demonstrate superior efficacy. Regarding treating fibrotic lung conditions, Nintedanib is a more compelling therapeutic option. |
| first_indexed | 2024-03-09T01:57:24Z |
| format | Article |
| id | doaj.art-118924fba4fb4a85b5d82cdcc5d7ff57 |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-09T01:57:24Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-118924fba4fb4a85b5d82cdcc5d7ff572023-12-08T12:34:12ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12586461258646Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertensionXin Zhang0Xin Zhang1Xiaoqian Deng2Liangliang Zhang3Pengbo Wang4Xia Tong5Yan Mo6Yuansheng Zhang7Yan Zhang8Chunheng Mo9Chunheng Mo10Lanlan Zhang11Department of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China (Airport) Hospital of Sichuan University (The First People’s Hospital of Shuangliu District, Chengdu), Chengdu, ChinaDepartment of Anesthesiology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, ChinaSchool of Professional Studies, Columbia University, New York, NY, United StatesDepartment of Gastroenterology, West China (Airport) Hospital of Sichuan University (The First People’s Hospital of Shuangliu District, Chengdu), Chengdu, ChinaDepartment of Neurology Medicine, The Aviation Industry Corporation of China (AVIC) 363 Hospital, Chengdu, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Gastroenterology, West China Hospital, Sichuan University, Chengdu, ChinaKey Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, West China Second University Hospital, Sichuan University, Chengdu, ChinaState Key Laboratory of Biotherapy, West China Second University Hospital, Sichuan University, Chengdu, ChinaDepartment of Pulmonary and Critical Care Medicine, State Key Laboratory of Respiratory Health and Multimorbidity, West China Hospital, Sichuan University, Chengdu, ChinaBackgroundThere is growing evidence that the lung is a target organ for injury in diabetes and hypertension. There are no studies on the status of the lungs, especially cellular subpopulations, and related functions in patients with diabetes, hypertension, and hypertension-diabetes after combined SARS-CoV-2 infection.MethodUsing single-cell meta-analysis in combination with bulk-RNA analysis, we identified three drug targets and potential receptors for SARS-CoV-2 infection in lung tissues from patients with diabetes, hypertension, and hypertension-diabetes, referred to as “co-morbid” patients. Using single-cell meta-analysis analysis in combination with bulk-RNA, we identified drug targets and potential receptors for SARS-CoV-2 infection in the three co-morbidities.ResultsThe single-cell meta-analysis of lung samples from SARS-CoV-2-infected individuals with diabetes, hypertension, and hypertension-diabetes comorbidity revealed an upregulation of fibroblast subpopulations in these disease conditions associated with a predictive decrease in lung function. To further investigate the response of fibroblasts to therapeutic targets in hypertension and diabetes, we analyzed 35 upregulated targets in both diabetes and hypertension. Interestingly, among these targets, five specific genes were upregulated in fibroblasts, suggesting their potential association with enhanced activation of endothelial cells. Furthermore, our investigation into the underlying mechanisms driving fibroblast upregulation indicated that KREMEN1, rather than ACE2, could be the receptor responsible for fibroblast activation. This finding adds novel insights into the molecular processes involved in fibroblast modulation in the context of SARS-CoV-2 infection within these comorbid conditions. Lastly, we compared the efficacy of Pirfenidone and Nintedanib as therapeutic interventions targeting fibroblasts prone to pulmonary fibrosis. Our findings suggest that Nintedanib may be a more suitable treatment option for COVID-19 patients with diabetes and hypertension who exhibit fibrotic lung lesions.ConclusionIn the context of SARS-CoV-2 infections, diabetes, hypertension, and their coexistence predominantly lead to myofibroblast proliferation. This phenomenon could be attributed to the upregulation of activated endothelial cells. Moreover, it is noteworthy that therapeutic interventions targeting hypertension-diabetes demonstrate superior efficacy. Regarding treating fibrotic lung conditions, Nintedanib is a more compelling therapeutic option.https://www.frontiersin.org/articles/10.3389/fendo.2023.1258646/fullSARS-CoV-2diabeteshypertensionendothelial cellsfibroblasts |
| spellingShingle | Xin Zhang Xin Zhang Xiaoqian Deng Liangliang Zhang Pengbo Wang Xia Tong Yan Mo Yuansheng Zhang Yan Zhang Chunheng Mo Chunheng Mo Lanlan Zhang Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension Frontiers in Endocrinology SARS-CoV-2 diabetes hypertension endothelial cells fibroblasts |
| title | Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension |
| title_full | Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension |
| title_fullStr | Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension |
| title_full_unstemmed | Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension |
| title_short | Single-cell RNA sequencing analysis of lung cells in COVID-19 patients with diabetes, hypertension, and comorbid diabetes-hypertension |
| title_sort | single cell rna sequencing analysis of lung cells in covid 19 patients with diabetes hypertension and comorbid diabetes hypertension |
| topic | SARS-CoV-2 diabetes hypertension endothelial cells fibroblasts |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1258646/full |
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