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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. Pathol...

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Autores principales: Liu, Shasha, Wang, Chengfang, Lu, Jianmin, Dai, Guangzheng, Che, Huixin, He, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212382/
https://www.ncbi.nlm.nih.gov/pubmed/34130526
http://dx.doi.org/10.1177/03000605211020641
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author Liu, Shasha
Wang, Chengfang
Lu, Jianmin
Dai, Guangzheng
Che, Huixin
He, Wei
author_facet Liu, Shasha
Wang, Chengfang
Lu, Jianmin
Dai, Guangzheng
Che, Huixin
He, Wei
author_sort Liu, Shasha
collection PubMed
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.
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spelling pubmed-82123822021-06-28 Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats Liu, Shasha Wang, Chengfang Lu, Jianmin Dai, Guangzheng Che, Huixin He, Wei J Int Med Res Prospective Clinical Research Report 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. SAGE Publications 2021-06-15 /pmc/articles/PMC8212382/ /pubmed/34130526 http://dx.doi.org/10.1177/03000605211020641 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by-nc/4.0/Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Prospective Clinical Research Report
Liu, Shasha
Wang, Chengfang
Lu, Jianmin
Dai, Guangzheng
Che, Huixin
He, Wei
Long-term inhibition of UCHL1 decreases hypertension and retinopathy in spontaneously hypertensive rats
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
topic Prospective Clinical Research Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8212382/
https://www.ncbi.nlm.nih.gov/pubmed/34130526
http://dx.doi.org/10.1177/03000605211020641
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