Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis
Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-10-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/21/21/8184 |
| _version_ | 1797549130713661440 |
|---|---|
| author | Jixiu Jin Tian Wang Woong Park Wenjia Li Won Kim Sung Kwang Park Kyung Pyo Kang |
| author_facet | Jixiu Jin Tian Wang Woong Park Wenjia Li Won Kim Sung Kwang Park Kyung Pyo Kang |
| author_sort | Jixiu Jin |
| collection | DOAJ |
| description | Yes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway. |
| first_indexed | 2024-03-10T15:10:01Z |
| format | Article |
| id | doaj.art-ca6e35d628a2480bad242ccc8b9c3fbb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:10:01Z |
| publishDate | 2020-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ca6e35d628a2480bad242ccc8b9c3fbb2023-11-20T19:25:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012121818410.3390/ijms21218184Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and FibrosisJixiu Jin0Tian Wang1Woong Park2Wenjia Li3Won Kim4Sung Kwang Park5Kyung Pyo Kang6Department of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaDepartment of Internal Medicine, Research Institute of Clinical Medicine, Jeonbuk National University Medical School, Jeonju 54907, KoreaYes-associated protein (YAP) activation after acute ischemic kidney injury might be related to interstitial fibrosis and impaired renal tubular regeneration. Verteporfin (VP) is a photosensitizer used in photodynamic therapy to treat age-related macular degeneration. In cancer cells, VP inhibits TEA domain family member (TEAD)-YAP interactions without light stimulation. The protective role of VP in unilateral ureteral obstruction (UUO)-induced renal fibrosis and related mechanisms remains unclear. In this study, we investigate the protective effects of VP on UUO-induced renal tubulointerstitial inflammation and fibrosis and its regulation of the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. We find that VP decreased the UUO-induced increase in tubular injury, inflammation, and extracellular matrix deposition in mice. VP also decreased myofibroblast activation and proliferation in UUO kidneys and NRK-49F cells by modulating Smad2 and Smad3 phosphorylation. Therefore, YAP inhibition might have beneficial effects on UUO-induced tubulointerstitial inflammation and fibrosis by regulating the TGF-β1/Smad signaling pathway.https://www.mdpi.com/1422-0067/21/21/8184kidney fibrosisinflammationmyofibroblast activationextracellular matrixHippo pathwayverteporfin |
| spellingShingle | Jixiu Jin Tian Wang Woong Park Wenjia Li Won Kim Sung Kwang Park Kyung Pyo Kang Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis International Journal of Molecular Sciences kidney fibrosis inflammation myofibroblast activation extracellular matrix Hippo pathway verteporfin |
| title | Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis |
| title_full | Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis |
| title_fullStr | Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis |
| title_full_unstemmed | Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis |
| title_short | Inhibition of Yes-Associated Protein by Verteporfin Ameliorates Unilateral Ureteral Obstruction-Induced Renal Tubulointerstitial Inflammation and Fibrosis |
| title_sort | inhibition of yes associated protein by verteporfin ameliorates unilateral ureteral obstruction induced renal tubulointerstitial inflammation and fibrosis |
| topic | kidney fibrosis inflammation myofibroblast activation extracellular matrix Hippo pathway verteporfin |
| url | https://www.mdpi.com/1422-0067/21/21/8184 |
| work_keys_str_mv | AT jixiujin inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT tianwang inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT woongpark inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT wenjiali inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT wonkim inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT sungkwangpark inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis AT kyungpyokang inhibitionofyesassociatedproteinbyverteporfinamelioratesunilateralureteralobstructioninducedrenaltubulointerstitialinflammationandfibrosis |