Ubiquitin C-terminal hydrolase L1 (UCHL1) regulates post-myocardial infarction cardiac fibrosis through glucose-regulated protein of 78 kDa (GRP78)
| العنوان: | Ubiquitin C-terminal hydrolase L1 (UCHL1) regulates post-myocardial infarction cardiac fibrosis through glucose-regulated protein of 78 kDa (GRP78) |
|---|---|
| المؤلفون: | Gerui Li, Yanggan Wang, Qian Lei, Zhijie Yan, Tao Yi, Hang Li, Zhan Lv |
| المصدر: | Scientific Reports, Vol 10, Iss 1, Pp 1-12 (2020) Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Cardiac function curve, medicine.medical_specialty, Glucose-regulated protein, Cardiac fibrosis, Myocardial Infarction, Cardiology, lcsh:Medicine, Ubiquitin C-Terminal Hydrolase, Article, Transforming Growth Factor beta1, Mice, Ubiquitin, Fibrosis, Internal medicine, Medicine, Animals, Myocardial infarction, Myofibroblasts, lcsh:Science, Endoplasmic Reticulum Chaperone BiP, Heat-Shock Proteins, Sulfonamides, Multidisciplinary, biology, business.industry, lcsh:R, medicine.disease, Up-Regulation, Disease Models, Animal, Thiazoles, Endocrinology, Cardiovascular diseases, biology.protein, Myocardial fibrosis, lcsh:Q, business, Ubiquitin Thiolesterase, Signal Transduction |
| الوصف: | Abnormal cardiac fibrosis indicates cardiac dysfunction and poor prognosis in myocardial infarction (MI) patients. Many studies have demonstrated that the ubiquitin proteasome system (UPS) plays a significant role in the pathogenesis of fibrosis. Ubiquitin C-terminal hydrolase L1 (UCHL1), a member of the UPS, is related to fibrosis in several heart diseases. However, whether UCHL1 regulates cardiac fibrosis following MI has yet to be determined. In the present study, we found that UCHL1 was dramatically increased in infarct hearts and TGF-β1-stimulated cardiac fibroblasts (CFs). Inhibition of UCHL1 with LDN57444 (LDN) reversed the myocardial fibrosis in post-MI heart and improved cardiac function. Treatment of LDN or UCHL1 siRNA abolished the TGF-β1-induced fibrotic response of CFs. We further identified GRP78 as an interactor of UCHL1 through screening using immunoprecipitation-mass spectrometer. We determined that UCHL1 interacted with glucose-regulated protein of 78 kDa (GRP78) and prompted GRP78 degradation via ubiquitination. Furthermore, we found that GRP78 was upregulated after UCHL1 knockdown and that the GRP78 inhibitor HA15 diminished the antifibrotic function exerted by UCHL1 knockdown in CFs stimulated with TGF-β1. This suggests that UCHL1 regulates cardiac fibrosis post MI through interactions with GRP78. This work identifies that the UCHL1-GRP78 axis is involved in cardiac fibrosis after MI. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09e2896e573e54bd3e2158920d0b1dedTest http://link.springer.com/article/10.1038/s41598-020-67746-4Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....09e2896e573e54bd3e2158920d0b1ded |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
|---|