Hepatocyte Growth Factor Inhibits Apoptosis by the Profibrotic Factor Angiotensin II via Extracellular Signal-regulated Kinase 1/2 in Endothelial Cells and Tissue Explants
| العنوان: | Hepatocyte Growth Factor Inhibits Apoptosis by the Profibrotic Factor Angiotensin II via Extracellular Signal-regulated Kinase 1/2 in Endothelial Cells and Tissue Explants |
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| المؤلفون: | Regina M. Day, Ognoon Mungunsukh, Young H. Lee, Ana P. Marquez |
| المصدر: | Molecular Biology of the Cell |
| بيانات النشر: | American Society for Cell Biology (ASCB), 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Blotting, Western, bcl-X Protein, Apoptosis, DNA Fragmentation, Biology, Cell Line, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Immunoprecipitation, RNA, Messenger, Molecular Biology, 030304 developmental biology, Mitogen-Activated Protein Kinase 1, 0303 health sciences, Mitogen-Activated Protein Kinase 3, L-Lactate Dehydrogenase, Caspase 3, Hepatocyte Growth Factor, Reverse Transcriptase Polymerase Chain Reaction, Kinase, Angiotensin II, Cytochromes c, Endothelial Cells, RNA-Binding Proteins, Articles, Cell Biology, MRNA stabilization, Phosphoproteins, Molecular biology, Signaling, Rats, 3. Good health, Cell biology, 030220 oncology & carcinogenesis, Cattle, Hepatocyte growth factor, Phosphatidylinositol 3-Kinase, Signal transduction, Nucleolin, Signal Transduction, medicine.drug |
| الوصف: | Hepatocyte growth factor (HGF) is a potent repair factor, promoting normal repair and preventing aberrant repair processes. Angiotensin (Ang) II is up-regulated in abnormal repair, such as fibrotic organ diseases. HGF also blocked Ang II-induced caspase apoptosis in primary endothelial cells and tissue explants in an extracellular signal-regulated kinase-dependent manner. Hepatocyte growth factor (HGF), an endogenous tissue repair factor, attenuates apoptosis in many primary cell types, but the mechanism is not completely understood. Our laboratory demonstrated that angiotensin (Ang) II activates the intrinsic apoptotic pathway in primary endothelial cells (ECs) via reduction of the antiapoptotic protein Bcl-xL. Ang II decreased Bcl-xL mRNA half-life by reducing its binding to nucleolin, a protein that normally binds a 3′ AU-rich region and stabilizes Bcl-xL mRNA. We hypothesized HGF may block apoptosis induced by Ang II. We used primary EC and ex vivo cultures of rat lung tissue to investigate HGF inhibition of Ang II-induced apoptosis. Our data indicated HGF abrogated Ang II-induced apoptosis by inhibiting cytochrome c release, caspase-3 activation, and DNA fragmentation. RNA-immunoprecipitation experiments demonstrated that HGF stabilized Bcl-xL mRNA by increasing nucleolin binding to the 3′-untranslated region that was associated with cytoplasmic localization of nucleolin. Cytoplasmic localization of nucleolin and Bcl-xL mRNA stabilization required HGF activation of extracellular signal-regulated kinase (ERK)1/2, but not phosphatidylinositol 3-kinase. HGF also blocked Ang II-induced caspase-3 activation and lactate dehydrogenase release in tissue explants in an ERK-dependent manner. |
| تدمد: | 1939-4586 1059-1524 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1768748cff9cfd911088eb8c82efad61Test https://doi.org/10.1091/mbc.e10-04-0341Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1768748cff9cfd911088eb8c82efad61 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19394586 10591524 |
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