Autophagic degradation of caveolin-1 promotes liver sinusoidal endothelial cells defenestration
| Autor: | Yun Huang, Xintao Zhu, Dan Wang, Ying Meng, Zuowei Ning, Guozhen Wang, Ye Hu, Yuehua You, Siyi Jin, Tingting Chen, Xiaoying Luo, Yang Li, Xu Li |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Liver Cirrhosis Male Cancer Research MAP Kinase Signaling System Proteolysis Immunology Caveolin 1 Article Rats Sprague-Dawley 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Fibrosis medicine Autophagy Animals Humans lcsh:QH573-671 Carbon Tetrachloride Actin Gene knockdown medicine.diagnostic_test Carbon Tetrachloride Poisoning lcsh:Cytology Bafilomycin Endothelial Cells Correction Cell Biology medicine.disease Actin cytoskeleton Cell biology Rats 030104 developmental biology chemistry Liver cardiovascular system Female |
| Zdroj: | Cell Death and Disease, Vol 9, Iss 5, Pp 1-17 (2018) Cell Death & Disease |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-018-0567-0 |
| Popis: | Autophagy, interacting with actin cytoskeleton and the NO-dependent pathway, may affect the phenotype and function of endothelial cells. Moreover, caveolin-1 (Cav-1), as a structure protein in liver sinusoidal endothelial cells (LSECs), is closely related to autophagy. Hence, we aim to explore the role of autophagic degradation of Cav-1 in LSECs defenestration. In vivo, we found the increase of autophagy in liver sinusoidal endothelium in human fibrotic liver. Furthermore, autophagy, degradation of Cav-1, and actin filament (F-actin) remodeling were triggered during the process of CCl4-induced LSECs defenestration; in contrast, autophagy inhibitor 3MA diminished the degradation of Cav-1 to maintain fenestrae and relieve CCl4-induced fibrosis. In vitro, during LSECs defenestration, the NO-dependent pathway was down-regulated through the reduction of the PI3K–AKT–MTOR pathway and initiation of autophagic degradation of Cav-1; while, these effects were aggravated by starvation. However, VEGF inhibited autophagic degradation of Cav-1 and F-actin remodeling to maintain LSECs fenestrae via activating the PI3K–AKT–MTOR pathway. Additionally, inhibiting autophagy, such as 3MA, bafilomycin, or ATG5-siRNA, could attenuate the depletion of Cav-1 and F-actin remodeling to maintain LSECs fenestrae and improve the NO-dependent pathway; in turn, eNOS-siRNA and L-NAME, for blocking the NO-dependent pathway, could elevate autophagic degradation of Cav-1 to aggravate defenestration. Finally, overexpressed Cav-1 rescued rapamycin-induced autophagic degradation of Cav-1 to maintain LSECs fenestrae; whereas knockdown of Cav-1 facilitated defenestration due to the activation of the AMPK-dependent autophagy. Consequently, autophagic degradation of Cav-1 promotes LSECs defenestration via inhibiting the NO-dependent pathway and F-actin remodeling. |
| Databáze: | OpenAIRE |
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