Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats
Objective To investigate the role of the deubiquitinase ubiquitin C-terminal hydrolase L1 (UCHL1) in hypertension and retinopathy in the spontaneously hypertensive rat (SHR). Methods Wistar–Kyoto (WKY) rats and SHRs were administered the UCHL1 inhibitor LDN57444 (20 μg/kg/day) for 4 months. Patholog...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2021-06-01
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| Series: | Journal of International Medical Research |
| Online Access: | https://doi.org/10.1177/03000605211020641 |
| _version_ | 1818402312122531840 |
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| author | Shasha Liu Chengfang Wang Jianmin Lu Guangzheng Dai Huixin Che Wei He |
| author_facet | Shasha Liu Chengfang Wang Jianmin Lu Guangzheng Dai Huixin Che Wei He |
| author_sort | Shasha Liu |
| collection | DOAJ |
| description | Objective To investigate the role of the deubiquitinase ubiquitin C-terminal hydrolase L1 (UCHL1) in hypertension and retinopathy in the spontaneously hypertensive rat (SHR). Methods Wistar–Kyoto (WKY) rats and SHRs were administered the UCHL1 inhibitor LDN57444 (20 μg/kg/day) for 4 months. Pathological changes were detected with hematoxylin and eosin, immunofluorescence, and dihydroethidium staining. The mRNA and protein expression of UCHL1 were examined by real-time PCR and immunoblotting analysis. Results At 6 months of age, SHRs showed significantly increased mRNA and protein levels of UCHL1 in the retina compared with WKY rats. Moreover, SHRs exhibited significantly increased central retinal thickness, inflammation, and reactive oxygen species production compared with WKY rats, and these effects were markedly attenuated by systemic administration of the UCHL1 inhibitor LDN57444. The beneficial effects of LDN57444 were possibly associated with reduced blood pressure and the inactivation of several signaling pathways. Conclusion UCHL1 is involved in hypertension and retinopathy in SHRs, suggesting that UCHL1 may be used as a potential therapeutic target for treating hypertensive retinopathy. |
| first_indexed | 2024-12-14T08:06:21Z |
| format | Article |
| id | doaj.art-bd9083155cc046a1b6e6e98445cbf9df |
| institution | Directory Open Access Journal |
| issn | 1473-2300 |
| language | English |
| last_indexed | 2024-12-14T08:06:21Z |
| publishDate | 2021-06-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Journal of International Medical Research |
| spelling | doaj.art-bd9083155cc046a1b6e6e98445cbf9df2022-12-21T23:10:10ZengSAGE PublishingJournal of International Medical Research1473-23002021-06-014910.1177/03000605211020641Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive ratsShasha LiuChengfang WangJianmin LuGuangzheng DaiHuixin CheWei HeObjective To investigate the role of the deubiquitinase ubiquitin C-terminal hydrolase L1 (UCHL1) in hypertension and retinopathy in the spontaneously hypertensive rat (SHR). Methods Wistar–Kyoto (WKY) rats and SHRs were administered the UCHL1 inhibitor LDN57444 (20 μg/kg/day) for 4 months. Pathological changes were detected with hematoxylin and eosin, immunofluorescence, and dihydroethidium staining. The mRNA and protein expression of UCHL1 were examined by real-time PCR and immunoblotting analysis. Results At 6 months of age, SHRs showed significantly increased mRNA and protein levels of UCHL1 in the retina compared with WKY rats. Moreover, SHRs exhibited significantly increased central retinal thickness, inflammation, and reactive oxygen species production compared with WKY rats, and these effects were markedly attenuated by systemic administration of the UCHL1 inhibitor LDN57444. The beneficial effects of LDN57444 were possibly associated with reduced blood pressure and the inactivation of several signaling pathways. Conclusion UCHL1 is involved in hypertension and retinopathy in SHRs, suggesting that UCHL1 may be used as a potential therapeutic target for treating hypertensive retinopathy.https://doi.org/10.1177/03000605211020641 |
| spellingShingle | Shasha Liu Chengfang Wang Jianmin Lu Guangzheng Dai Huixin Che Wei He Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats Journal of International Medical Research |
| title | Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| title_full | Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| title_fullStr | Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| title_full_unstemmed | Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| title_short | Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| title_sort | long term inhibition of uchl1 decreases hypertension and retinopathy in spontaneously hypertensive rats |
| url | https://doi.org/10.1177/03000605211020641 |
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