Hypoxia maintains the fenestration of liver sinusoidal endothelial cells and promotes their proliferation through the SENP1/HIF-1α/VEGF signaling axis
| Autor: | Qing Zhe, Shikun Yang, Zhong Zeng, Hanfei Huang, Tingfeng Ming, Jie Lin, Jian Duan, Bo Yuan |
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| Rok vydání: | 2021 |
| Předmět: |
Male
Vascular Endothelial Growth Factor A 0301 basic medicine SENP1 medicine.medical_treatment VEGF receptors Biophysics Down-Regulation Biochemistry Mice 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Animals VEGF signaling Molecular Biology Cell Proliferation Protease biology Chemistry Endothelial Cells Cell Biology Hypoxia (medical) Hypoxia-Inducible Factor 1 alpha Subunit Cell Hypoxia Liver regeneration Cell biology Mice Inbred C57BL Cysteine Endopeptidases 030104 developmental biology Liver 030220 oncology & carcinogenesis biology.protein medicine.symptom Function (biology) Signal Transduction |
| Zdroj: | Biochemical and Biophysical Research Communications. 540:42-50 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.12.104 |
| Popis: | Liver sinusoidal endothelial cells (LSECs), which play a very critical role in liver regeneration, function in hypoxic environments, but few studies have elucidated the specific mechanism. As a hypoxia-sensitive gene, Sentrin/SUMO-specific protease 1(SENP1) is upregulated in solid tumors due to hypoxia and promotes tumor proliferation. We speculate that LSECs may upregulate SENP1 in hypoxic environments and that SENP1 may act on downstream genes to allow the cells to adapt to the hypoxic environment. To elucidate the reasons for the survival of LSECs under hypoxia, we designed experiments to explore the possible mechanism. First, we cultured murine LSECs in hypoxic conditions for a certain time (24 h and 72 h), and then, we observed that the proliferation ability of the hypoxia group was higher than that of the normoxia group, and the number of unique fenestrae of the LSECs in the hypoxia group was more than that of the LSECs in the normoxia group. Then, we divided the LSECs into several groups for hypoxic culture for time points (6 h, 12 h, 24 h, 36 h, and 72 h), and we found that the expression of SENP1, HIF-1α and VEGF was significantly upregulated. Then, we silenced SENP1 and HIF-1α with si-SENP1 and si–HIF–1α, respectively. SENP1, HIF-1α and VEGF were significantly downregulated, as determined by RT-PCR, WB and ELISA. Unexpectedly, the proliferation activity of the LSECs decreased and the fenestrae disappeared more in the si-SENP1 and si–HIF–1α groups than in the control group. It is concluded that LSECs cultured under hypoxic conditions may maintain fenestrae and promote proliferation through the SENP1/HIF-1α/VEGF signaling axis, thereby adapting to the hypoxic environment. |
| Databáze: | OpenAIRE |
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