Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway
Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensi...
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| Format: | Article |
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Frontiers Media S.A.
2022-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.964370/full |
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| author | Yan-Ni Wang Hong-Jiao Liu Li-Li Ren Ping Suo Liang Zou Ya-Mei Zhang Xiao-Yong Yu Ying-Yong Zhao Ying-Yong Zhao Ying-Yong Zhao |
| author_facet | Yan-Ni Wang Hong-Jiao Liu Li-Li Ren Ping Suo Liang Zou Ya-Mei Zhang Xiao-Yong Yu Ying-Yong Zhao Ying-Yong Zhao Ying-Yong Zhao |
| author_sort | Yan-Ni Wang |
| collection | DOAJ |
| description | Chronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensin system (RAS) has been used as a first-line standard therapy in patients with hypertension and CKD, patients still progress towards end-stage kidney disease, which might be closely associated with compensatory renin expression subsequent to RAS blockade through a homeostatic mechanism. The Wnt/β-catenin signalling pathway is the master upstream regulator that controls multiple intrarenal RAS genes. As Wnt/β-catenin regulates multiple RAS genes, we inferred that this pathway might also be implicated in blood pressure control. Therefore, discovering new medications to synchronously target multiple RAS genes is necessary and essential for the effective treatment of patients with CKD. We hypothesized that Shenkang injection (SKI), which is widely used to treat CKD patients, might ameliorate CKD by inhibiting the activation of multiple RAS genes via the Wnt/β-catenin signalling pathway. To test this hypothesis, we used adenine-induced CKD rats and angiotensin II (AngII)-induced HK-2 and NRK-49F cells. Treatment with SKI inhibited renal function decline, hypertension and renal fibrosis. Mechanistically, SKI abrogated the increased protein expression of multiple RAS elements, including angiotensin-converting enzyme and angiotensin II type 1 receptor, as well as Wnt1, β-catenin and downstream target genes, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in adenine-induced rats, which was verified in AngII-induced HK-2 and NRK-49F cells. Similarly, our results further indicated that treatment with rhein isolated from SKI attenuated renal function decline and epithelial-to-mesenchymal transition and repressed RAS activation and the hyperactive Wnt/β-catenin signalling pathway in both adenine-induced rats and AngII-induced HK-2 and NRK-49F cells. This study first revealed that SKI repressed epithelial-to-mesenchymal transition by synchronously targeting multiple RAS elements by blocking the hyperactive Wnt/β-catenin signalling pathway. |
| first_indexed | 2024-04-11T21:58:45Z |
| format | Article |
| id | doaj.art-b51879d632fe4c1dbdca778e5abb12c0 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T21:58:45Z |
| publishDate | 2022-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-b51879d632fe4c1dbdca778e5abb12c02022-12-22T04:01:00ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-08-011310.3389/fphar.2022.964370964370Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathwayYan-Ni Wang0Hong-Jiao Liu1Li-Li Ren2Ping Suo3Liang Zou4Ya-Mei Zhang5Xiao-Yong Yu6Ying-Yong Zhao7Ying-Yong Zhao8Ying-Yong Zhao9Faculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi, ChinaFaculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi, ChinaFaculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi, ChinaFaculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi, ChinaKey Disciplines Team of Clinical Pharmacy, School of Food and Bioengineering, Affiliated Hospital of Chengdu University, Chengdu University, Chengdu, Sichuan, ChinaClinical Genetics Laboratory, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu, Sichuan, ChinaDepartment of Nephrology, Shaanxi Traditional Chinese Medicine Hospital, Xi’an, Shaanxi, ChinaFaculty of Life Science and Medicine, Northwest University, Xi’an, Shaanxi, ChinaClinical Genetics Laboratory, Affiliated Hospital and Clinical Medical College of Chengdu University, Chengdu, Sichuan, ChinaSchool of Pharmacy, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, ChinaChronic kidney disease (CKD) is a major worldwide public health problem. The increase in the number of patients with CKD and end-stage kidney disease requesting renal dialysis or transplantation will progress to epidemic proportions in the next several decades. Although blocking the renin-angiotensin system (RAS) has been used as a first-line standard therapy in patients with hypertension and CKD, patients still progress towards end-stage kidney disease, which might be closely associated with compensatory renin expression subsequent to RAS blockade through a homeostatic mechanism. The Wnt/β-catenin signalling pathway is the master upstream regulator that controls multiple intrarenal RAS genes. As Wnt/β-catenin regulates multiple RAS genes, we inferred that this pathway might also be implicated in blood pressure control. Therefore, discovering new medications to synchronously target multiple RAS genes is necessary and essential for the effective treatment of patients with CKD. We hypothesized that Shenkang injection (SKI), which is widely used to treat CKD patients, might ameliorate CKD by inhibiting the activation of multiple RAS genes via the Wnt/β-catenin signalling pathway. To test this hypothesis, we used adenine-induced CKD rats and angiotensin II (AngII)-induced HK-2 and NRK-49F cells. Treatment with SKI inhibited renal function decline, hypertension and renal fibrosis. Mechanistically, SKI abrogated the increased protein expression of multiple RAS elements, including angiotensin-converting enzyme and angiotensin II type 1 receptor, as well as Wnt1, β-catenin and downstream target genes, including Snail1, Twist, matrix metalloproteinase-7, plasminogen activator inhibitor-1 and fibroblast-specific protein 1, in adenine-induced rats, which was verified in AngII-induced HK-2 and NRK-49F cells. Similarly, our results further indicated that treatment with rhein isolated from SKI attenuated renal function decline and epithelial-to-mesenchymal transition and repressed RAS activation and the hyperactive Wnt/β-catenin signalling pathway in both adenine-induced rats and AngII-induced HK-2 and NRK-49F cells. This study first revealed that SKI repressed epithelial-to-mesenchymal transition by synchronously targeting multiple RAS elements by blocking the hyperactive Wnt/β-catenin signalling pathway.https://www.frontiersin.org/articles/10.3389/fphar.2022.964370/fullchronic kidney diseaserenal fibrosisShenkang injectionrheinrenin-angiotensin systemWnt/β-catenin signalling pathway |
| spellingShingle | Yan-Ni Wang Hong-Jiao Liu Li-Li Ren Ping Suo Liang Zou Ya-Mei Zhang Xiao-Yong Yu Ying-Yong Zhao Ying-Yong Zhao Ying-Yong Zhao Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway Frontiers in Pharmacology chronic kidney disease renal fibrosis Shenkang injection rhein renin-angiotensin system Wnt/β-catenin signalling pathway |
| title | Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway |
| title_full | Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway |
| title_fullStr | Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway |
| title_full_unstemmed | Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway |
| title_short | Shenkang injection improves chronic kidney disease by inhibiting multiple renin-angiotensin system genes by blocking the Wnt/β-catenin signalling pathway |
| title_sort | shenkang injection improves chronic kidney disease by inhibiting multiple renin angiotensin system genes by blocking the wnt β catenin signalling pathway |
| topic | chronic kidney disease renal fibrosis Shenkang injection rhein renin-angiotensin system Wnt/β-catenin signalling pathway |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.964370/full |
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