Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis
Objective 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. Methods A mouse model of hypoxic lung injury was established by being placed in...
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Editorial Office of Journal of Army Medical University
2025-03-01
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| Series: | 陆军军医大学学报 |
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| Online Access: | https://aammt.tmmu.edu.cn/html/202502051.html |
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| author | LIU Paiyu LIU Paiyu Department of Psychiatry and Psychology， No. 991 Hospital of Joint Logistic Support Force of PLA， Xiangyang， Hubei ZENG Jitao |
| author_facet | LIU Paiyu LIU Paiyu Department of Psychiatry and Psychology， No. 991 Hospital of Joint Logistic Support Force of PLA， Xiangyang， Hubei ZENG Jitao |
| author_sort | LIU Paiyu |
| collection | DOAJ |
| description | Objective 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. Methods 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. Results 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). Conclusion 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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| format | Article |
| id | doaj-art-506586c6ee3d466a8a30077930d7b82b |
| institution | Kabale University |
| issn | 2097-0927 |
| language | zho |
| publishDate | 2025-03-01 |
| publisher | Editorial Office of Journal of Army Medical University |
| record_format | Article |
| series | 陆军军医大学学报 |
| spelling | doaj-art-506586c6ee3d466a8a30077930d7b82b2025-08-20T03:41:10ZzhoEditorial Office of Journal of Army Medical University陆军军医大学学报2097-09272025-03-0147649850510.16016/j.2097-0927.202502051Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axisLIU Paiyu 0LIU Paiyu 1Department of Psychiatry and Psychology， No. 991 Hospital of Joint Logistic Support Force of PLA， Xiangyang， Hubei2ZENG Jitao 3 Department of Pathophysiology， Faculty of High Altitude Military Medicine， Army Medical University （Third Military Medical University）， ChongqingDepartment of Psychiatry and Psychology， No. 991 Hospital of Joint Logistic Support Force of PLA， Xiangyang， HubeiDepartment of Pathophysiology， Faculty of High Altitude Military Medicine， Army Medical University （Third Military Medical University）， ChongqingReproductive Medical Center， First Affiliated Hospital， Army Medical University （Third Military Medical University）， Chongqing， ChinaObjective 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. Methods 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. Results 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). Conclusion 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. https://aammt.tmmu.edu.cn/html/202502051.htmlhypoxiaalveolar epithelial cellstazhistone variant of histone h2aproliferation |
| spellingShingle | LIU Paiyu LIU Paiyu Department of Psychiatry and Psychology， No. 991 Hospital of Joint Logistic Support Force of PLA， Xiangyang， Hubei ZENG Jitao Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis 陆军军医大学学报 hypoxia alveolar epithelial cells taz histone variant of histone h2a proliferation |
| title | Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis |
| title_full | Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis |
| title_fullStr | Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis |
| title_full_unstemmed | Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis |
| title_short | Hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin H2A.Z deposition through TAZ-H2A.Z axis |
| title_sort | hypoxia promotes proliferation of alveolar epithelial cells by regulating chromatin h2a z deposition through taz h2a z axis |
| topic | hypoxia alveolar epithelial cells taz histone variant of histone h2a proliferation |
| url | https://aammt.tmmu.edu.cn/html/202502051.html |
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