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Outline
To explore the role and underlying mechanism of the transcriptional coactivator with PDZ-binding motif (TAZ) and a histone variant of acute histone H2A (H2A.Z) in the repair of hypoxia-induced lung injury.
A mouse model of hypoxic lung injury was established by being placed in a hypoxia chamber (simulating an altitude of 5 800 m) for 4 d. HE staining was used to observe the severity of lung injury. A hypoxia model of murine alveolar epithelial cells (murine lung epithelial-12, MLE12) was constructed by treating the cells in a hypoxia workstation (1%O2 concentration) for 24 h. Western blotting was employed to detect TAZ expression. The proliferation of alveolar epithelial cells (AECs) was evaluated by CCK-8 assay. Co-immunoprecipitation (Co-IP) assay was utilized to verify the interaction between TAZ and H2A.Z. CUT&Tag sequencing was performed to determine the effect of TAZ on the chromatin deposition of H2A.Z.
Hypoxia significantly induced alveolar atrophy and inflammatory infiltration in mouse lung tissues(P<0.01). Hypoxia significantly up-regulated the protein level of TAZ in MLE12 cells (P<0.05). CCK-8 assay showed that knockdown of TAZ significantly reduced the proliferative capacity of AECs (P<0.01). Co-IP assay confirmed the physical interaction between TAZ and H2A.Z. CUT&Tag sequencing revealed that hypoxia promoted the deposition of H2A.Z on chromatin (31 817 peaks under normoxia, 44 078 peaks under hypoxia), which was partially reversed by TAZ knockdown (37 840 peaks).
Hypoxia significantly up-regulates the expression of TAZ, which combines with H2A.Z and promotes the deposition of H2A.Z on chromatin, thus enhancing the proliferation of AECs in response to hypoxic injury.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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