CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s
Abstract Background Functional alveolar regeneration is essential for the restoration of normal lung homeostasis after acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Lung is a relatively quiescent organ and a variety of stem cells are recruited to participate in lung repair...
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| Format: | Article |
| Language: | English |
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BMC
2023-09-01
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| Series: | Respiratory Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12931-023-02512-4 |
| _version_ | 1797556991173853184 |
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| author | Jianhui Sun Huacai Zhang Di Liu Wenyi Liu Juan Du Dalin Wen Luoxi Li Anqiang Zhang Jianxin Jiang Ling Zeng |
| author_facet | Jianhui Sun Huacai Zhang Di Liu Wenyi Liu Juan Du Dalin Wen Luoxi Li Anqiang Zhang Jianxin Jiang Ling Zeng |
| author_sort | Jianhui Sun |
| collection | DOAJ |
| description | Abstract Background Functional alveolar regeneration is essential for the restoration of normal lung homeostasis after acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Lung is a relatively quiescent organ and a variety of stem cells are recruited to participate in lung repair and regeneration after lung tissue injury. However, there is still no effective method for promoting the proliferation of endogenous lung stem cells to promote repair and regeneration. Methods Using protein mass spectrometry analysis, we analyzed the microenvironment after acute lung injury. RNA sequencing and image cytometry were used in the alveolar epithelial type 2 cells (AEC2s) subgroup identification. Then we used Sftpc+AEC2 lineage tracking mice and purified AEC2s to further elucidate the molecular mechanism by which CTGF regulates AEC2s proliferation both in vitro and in vivo. Bronchoalveolar lavage fluid (BALF) from thirty ARDS patients who underwent bronchoalveolar lavage was collected for the analysis of the correlation between the expressing of Krt5 in BALF and patients’ prognosis. Results Here, we elucidate that AEC2s are the main facultative stem cells of the distal lung after ALI and ARDS. The increase of connective tissue growth factor (CTGF) in the microenvironment after ALI promoted the proliferation of AEC2s subpopulations. Proliferated AEC2s rapidly expanded and differentiated into alveolar epithelial type 1 cells (AEC1s) in the regeneration after ALI. CTGF initiates the phosphorylation of LRP6 by promoting the interaction between Krt5 and LRP6 of AEC2s, thus activating the Wnt signaling pathway, which is the molecular mechanism of CTGF promoting the proliferation of AEC2s subpopulation. Conclusions Our study verifies that CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of AEC2s subpopulation. |
| first_indexed | 2024-03-10T17:10:56Z |
| format | Article |
| id | doaj.art-44e113c3ff3e45bbada1d0beb861cfb0 |
| institution | Directory Open Access Journal |
| issn | 1465-993X |
| language | English |
| last_indexed | 2024-03-10T17:10:56Z |
| publishDate | 2023-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-44e113c3ff3e45bbada1d0beb861cfb02023-11-20T10:40:22ZengBMCRespiratory Research1465-993X2023-09-0124111610.1186/s12931-023-02512-4CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2sJianhui Sun0Huacai Zhang1Di Liu2Wenyi Liu3Juan Du4Dalin Wen5Luoxi Li6Anqiang Zhang7Jianxin Jiang8Ling Zeng9Department of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityDepartment of Trauma Medical Center, Daping Hospital, State Key Laboratory of Trauma, Burns and Combined Injury, Army Medical UniversityAbstract Background Functional alveolar regeneration is essential for the restoration of normal lung homeostasis after acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Lung is a relatively quiescent organ and a variety of stem cells are recruited to participate in lung repair and regeneration after lung tissue injury. However, there is still no effective method for promoting the proliferation of endogenous lung stem cells to promote repair and regeneration. Methods Using protein mass spectrometry analysis, we analyzed the microenvironment after acute lung injury. RNA sequencing and image cytometry were used in the alveolar epithelial type 2 cells (AEC2s) subgroup identification. Then we used Sftpc+AEC2 lineage tracking mice and purified AEC2s to further elucidate the molecular mechanism by which CTGF regulates AEC2s proliferation both in vitro and in vivo. Bronchoalveolar lavage fluid (BALF) from thirty ARDS patients who underwent bronchoalveolar lavage was collected for the analysis of the correlation between the expressing of Krt5 in BALF and patients’ prognosis. Results Here, we elucidate that AEC2s are the main facultative stem cells of the distal lung after ALI and ARDS. The increase of connective tissue growth factor (CTGF) in the microenvironment after ALI promoted the proliferation of AEC2s subpopulations. Proliferated AEC2s rapidly expanded and differentiated into alveolar epithelial type 1 cells (AEC1s) in the regeneration after ALI. CTGF initiates the phosphorylation of LRP6 by promoting the interaction between Krt5 and LRP6 of AEC2s, thus activating the Wnt signaling pathway, which is the molecular mechanism of CTGF promoting the proliferation of AEC2s subpopulation. Conclusions Our study verifies that CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of AEC2s subpopulation.https://doi.org/10.1186/s12931-023-02512-4Acute lung injuryAcute respiratory distress syndromeAlveolar regenerationConnective tissue growth factorAlveolar epithelial type 2 cellsAlveolar epithelial type 1 cells |
| spellingShingle | Jianhui Sun Huacai Zhang Di Liu Wenyi Liu Juan Du Dalin Wen Luoxi Li Anqiang Zhang Jianxin Jiang Ling Zeng CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s Respiratory Research Acute lung injury Acute respiratory distress syndrome Alveolar regeneration Connective tissue growth factor Alveolar epithelial type 2 cells Alveolar epithelial type 1 cells |
| title | CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s |
| title_full | CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s |
| title_fullStr | CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s |
| title_full_unstemmed | CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s |
| title_short | CTGF promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of AEC2s |
| title_sort | ctgf promotes the repair and regeneration of alveoli after acute lung injury by promoting the proliferation of subpopulation of aec2s |
| topic | Acute lung injury Acute respiratory distress syndrome Alveolar regeneration Connective tissue growth factor Alveolar epithelial type 2 cells Alveolar epithelial type 1 cells |
| url | https://doi.org/10.1186/s12931-023-02512-4 |
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