Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor
Introduction: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. Objective: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. Methods and Results: Collecting d...
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Elsevier
2025-02-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2090123224000535 |
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| author | Ke Sun Yong-Li Wang Chen-Chen Hou Da Shang Lin-Juan Du Lan Bai Xing-Yu Zhang Chuan-Ming Hao Sheng-Zhong Duan |
| author_facet | Ke Sun Yong-Li Wang Chen-Chen Hou Da Shang Lin-Juan Du Lan Bai Xing-Yu Zhang Chuan-Ming Hao Sheng-Zhong Duan |
| author_sort | Ke Sun |
| collection | DOAJ |
| description | Introduction: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. Objective: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. Methods and Results: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model. KO mice also showed significantly higher BP than littermate control (LC) mice in deoxycorticosterone acetate (DOCA)-salt model. Further study showed that collecting duct NCOR1 deficiency aggravated volume and sodium retention after saline challenge. Among the sodium transporter in the collecting duct, the expression of the three epithelial sodium channel (ENaC) subunits was markedly increased in the renal medulla of KO mice. Consistently, BP in Ang II-infused KO mice decreased significantly to the similar level as those in LC mice after amiloride treatment. ChIP analysis revealed that NCOR1 deficiency increased the enrichment of mineralocorticoid receptor (MR) on the promoters of the three ENaC genes in primary inner medulla collecting duct (IMCD) cells. Co-IP results showed interaction between NCOR1 and MR, and luciferase reporter results demonstrated that NCOR1 inhibited the transcriptional activity of MR. Knockdown of MR eliminated the increased ENaC expression in primary IMCD cells isolated from KO mice. Finally, BP was significantly decreased in Ang II-infused KO mice after treatment of MR antagonist spironolactone and the difference between LC and KO mice was abolished. Conclusions: NCOR1 interacts with MR to control ENaC activity in the collecting duct and to regulate sodium reabsorption and ultimately BP. Targeting NCOR1 might be a promising tactic to interrupt the volume and sodium retention of the collecting duct in hypertension. |
| format | Article |
| id | doaj-art-f9e0aaa9584648d9987339eaef2ec93e |
| institution | Kabale University |
| issn | 2090-1232 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj-art-f9e0aaa9584648d9987339eaef2ec93e2025-01-18T05:04:16ZengElsevierJournal of Advanced Research2090-12322025-02-01687587Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptorKe Sun0Yong-Li Wang1Chen-Chen Hou2Da Shang3Lin-Juan Du4Lan Bai5Xing-Yu Zhang6Chuan-Ming Hao7Sheng-Zhong Duan8Department of Nephrology, Zhejiang University Medical College Affiliated Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province 310016, China; Division of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaDepartment of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, ChinaDepartment of Respiratory and Critical Care Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, ChinaDivision of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, ChinaLaboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, ChinaLaboratory of Oral Microbiota and Systemic Diseases, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai 200125, China; National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai 200011, ChinaDepartment of Cardiology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, ChinaDivision of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China; Corresponding authors at: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China (S.-Z. Duan). Division of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China (C.-M. Hao).Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine; State Key Laboratory of Transvascular Implantation Devices, Hangzhou, Zhejiang 310000, China; Corresponding authors at: Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310000, China (S.-Z. Duan). Division of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China (C.-M. Hao).Introduction: Nuclear receptor corepressor 1(NCOR1) is reported to play crucial roles in cardiovascular diseases, but its function in the kidney has remained obscure. Objective: We aim to elucidate the role of collecting duct NCOR1 in blood pressure (BP) regulation. Methods and Results: Collecting duct NCOR1 knockout (KO) mice manifested increased BP and aggravated vascular and renal injury in an angiotensin II (Ang II)-induced hypertensive model. KO mice also showed significantly higher BP than littermate control (LC) mice in deoxycorticosterone acetate (DOCA)-salt model. Further study showed that collecting duct NCOR1 deficiency aggravated volume and sodium retention after saline challenge. Among the sodium transporter in the collecting duct, the expression of the three epithelial sodium channel (ENaC) subunits was markedly increased in the renal medulla of KO mice. Consistently, BP in Ang II-infused KO mice decreased significantly to the similar level as those in LC mice after amiloride treatment. ChIP analysis revealed that NCOR1 deficiency increased the enrichment of mineralocorticoid receptor (MR) on the promoters of the three ENaC genes in primary inner medulla collecting duct (IMCD) cells. Co-IP results showed interaction between NCOR1 and MR, and luciferase reporter results demonstrated that NCOR1 inhibited the transcriptional activity of MR. Knockdown of MR eliminated the increased ENaC expression in primary IMCD cells isolated from KO mice. Finally, BP was significantly decreased in Ang II-infused KO mice after treatment of MR antagonist spironolactone and the difference between LC and KO mice was abolished. Conclusions: NCOR1 interacts with MR to control ENaC activity in the collecting duct and to regulate sodium reabsorption and ultimately BP. Targeting NCOR1 might be a promising tactic to interrupt the volume and sodium retention of the collecting duct in hypertension.http://www.sciencedirect.com/science/article/pii/S2090123224000535HypertensionCollecting ductNCOR1MRENaC |
| spellingShingle | Ke Sun Yong-Li Wang Chen-Chen Hou Da Shang Lin-Juan Du Lan Bai Xing-Yu Zhang Chuan-Ming Hao Sheng-Zhong Duan Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor Journal of Advanced Research Hypertension Collecting duct NCOR1 MR ENaC |
| title | Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor |
| title_full | Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor |
| title_fullStr | Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor |
| title_full_unstemmed | Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor |
| title_short | Collecting duct NCOR1 controls blood pressure by regulating mineralocorticoid receptor |
| title_sort | collecting duct ncor1 controls blood pressure by regulating mineralocorticoid receptor |
| topic | Hypertension Collecting duct NCOR1 MR ENaC |
| url | http://www.sciencedirect.com/science/article/pii/S2090123224000535 |
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