Renal asymmetric dimethylarginine inhibits fibrosis
Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | FEBS Open Bio |
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| Online Access: | https://doi.org/10.1002/2211-5463.12949 |
| _version_ | 1828415335717404672 |
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| author | Ming Wu Meijie Yuan Yanzhe Wang Bo Tan Di Huang Chen Wang Yun Zou Chaoyang Ye |
| author_facet | Ming Wu Meijie Yuan Yanzhe Wang Bo Tan Di Huang Chen Wang Yun Zou Chaoyang Ye |
| author_sort | Ming Wu |
| collection | DOAJ |
| description | Chronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect in vivo experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis in vivo. Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, α‐smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson’s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of Ddah1 or Ddah2 increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson’s staining. Thus, our in vivo data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO. |
| first_indexed | 2024-12-10T13:43:02Z |
| format | Article |
| id | doaj.art-086349ef320c443d93ba51cad1a7bf53 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-12-10T13:43:02Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-086349ef320c443d93ba51cad1a7bf532022-12-22T01:46:34ZengWileyFEBS Open Bio2211-54632020-10-0110102003200910.1002/2211-5463.12949Renal asymmetric dimethylarginine inhibits fibrosisMing Wu0Meijie Yuan1Yanzhe Wang2Bo Tan3Di Huang4Chen Wang5Yun Zou6Chaoyang Ye7Department of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaClinical Pharmacokinetic Laboratory Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaDepartment of Nephrology TCM Institute of Kidney Disease of Shanghai University of Traditional Chinese Medicine Key Laboratory of Liver and Kidney Diseases Ministry of Education Shanghai Key Laboratory of Traditional Chinese Clinical Medicine Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine ChinaChronic kidney disease (CKD) is a worldwide public health problem that is caused by repeated injuries to the glomerulus or renal tubules. Renal fibrosis commonly accompanies CKD, and it is histologically characterized by excessive deposition of extracellular matrix proteins, such as fibronectin and collagen I, in interstitial areas. Indirect in vivo experimental data suggest that renal asymmetric dimethylarginine (ADMA) exerts antifibrotic activity in CKD. In this study, we aimed to demonstrate that renal ADMA has a direct effect on fibrosis in vivo. Normal saline, ADMA, nonsense control siRNA, Ddah1 siRNA or Ddah2 siRNA was administered into the kidney through the left ureter in a mouse model of unilateral ureteral obstruction (UUO). UUO kidneys were harvested at day 1 or 7. Western blotting was performed to assess the expression of ADMA, DDAH1 and DDAH2 and the expression of fibrotic markers, such as fibronectin, collagen I, α‐smooth muscle actin, phosphorylation of Smad3 and connective tissue growth factor. Masson’s trichrome staining was used to further evaluate renal fibrosis. We observed that intrarenal administration of ADMA increased the renal accumulation of ADMA and attenuated renal fibrosis at days 1 and 7. Knockdown of Ddah1 or Ddah2 increased the amount of ADMA in UUO kidneys and inhibited the expression of fibrotic proteins at days 1 and 7, which was further confirmed by Masson’s staining. Thus, our in vivo data suggest that renal ADMA exerts direct antifibrotic effects in a mouse model of UUO.https://doi.org/10.1002/2211-5463.12949ADMACKDDDAH‐1DDAH‐2renal fibrosis |
| spellingShingle | Ming Wu Meijie Yuan Yanzhe Wang Bo Tan Di Huang Chen Wang Yun Zou Chaoyang Ye Renal asymmetric dimethylarginine inhibits fibrosis FEBS Open Bio ADMA CKD DDAH‐1 DDAH‐2 renal fibrosis |
| title | Renal asymmetric dimethylarginine inhibits fibrosis |
| title_full | Renal asymmetric dimethylarginine inhibits fibrosis |
| title_fullStr | Renal asymmetric dimethylarginine inhibits fibrosis |
| title_full_unstemmed | Renal asymmetric dimethylarginine inhibits fibrosis |
| title_short | Renal asymmetric dimethylarginine inhibits fibrosis |
| title_sort | renal asymmetric dimethylarginine inhibits fibrosis |
| topic | ADMA CKD DDAH‐1 DDAH‐2 renal fibrosis |
| url | https://doi.org/10.1002/2211-5463.12949 |
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