Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid
Impaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial feat...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/11/5/817 |
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| author | Chen-Liang Tsai Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Yi-Wen Wang Kai-Chieh Chou Ming-Hsien Chiang Yu-Ling Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Hung-Yi Lin Tse-Bin Yang Chih-Feng Chian |
| author_facet | Chen-Liang Tsai Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Yi-Wen Wang Kai-Chieh Chou Ming-Hsien Chiang Yu-Ling Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Hung-Yi Lin Tse-Bin Yang Chih-Feng Chian |
| author_sort | Chen-Liang Tsai |
| collection | DOAJ |
| description | Impaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial features during cutaneous wound healing. Therefore, the current study aimed to investigate the effect of pleural fluid on cutaneous wound closure in vitro and in vivo using HaCaT keratinocytes and a full-thickness skin wound model, respectively. Both heart-failure-associated pleural fluid (HFPF) and LCPF were sequentially centrifuged and filtered to obtain a cell-free status. Treatment with HFPF and LCPF homogeneously induced HaCaT proliferation with cell cycle progression, migration, and MMP2 upregulation. Western blotting revealed increased PI3K/Akt phosphorylation and VEGFR2/VEGFA expression in HaCaT cells. When treated with the PI3K inhibitor, LCPF-induced keratinocyte proliferation was attenuated with decreased pS6 levels. By applying the VEGFR2 inhibitor, LCPF-induced keratinocyte proliferation was ameliorated by pS6 and MMP2 downregulation. The effect of LCPF-induced cell junction rearrangement was disrupted by co-treatment with a VEGFR2 inhibitor. Compared with a 0.9% saline dressing, LCPF significantly accelerated wound closure and re-epithelization when used as a dressing material in a full-thickness wound model. Histological analysis revealed increased neo-epidermis thickness and dermis collagen synthesis in the LCPF-treated group. Furthermore, LCPF treatment activated basal keratinocytes at the wound edge with the upregulation of Ki-67, VEGFA, and MMP2. Our preliminaries provided the benefit of wet dressing with pleural fluid to improve cutaneous wound closure through enhanced re-epithelization and disclosed future autologous application in cancer wound treatment. |
| first_indexed | 2024-03-09T20:43:21Z |
| format | Article |
| id | doaj.art-068c015f969f4342bad2ff97adeb34bf |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T20:43:21Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-068c015f969f4342bad2ff97adeb34bf2023-11-23T22:50:43ZengMDPI AGCells2073-44092022-02-0111581710.3390/cells11050817Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural FluidChen-Liang Tsai0Chih-Ying Changchien1Ying Chen2Hsin-Han Chang3Wen-Chiuan Tsai4Yi-Wen Wang5Kai-Chieh Chou6Ming-Hsien Chiang7Yu-Ling Tsai8Hao-Chung Tsai9Chieh-Yung Wang10Ming-Sheng Shen11Li-Ting Cheng12Hung-Yi Lin13Tse-Bin Yang14Chih-Feng Chian15Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Biology and Anatomy, National Defense Medical Center, Taipei 114, TaiwanDepartment of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Division of Chest Medicine, Tri-Service General Hospital Songshan Branch, Taipei 105, TaiwanDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Taichung Armed Force General Hospital, Taichung 411, TaiwanDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanDepartment of Internal Medicine, Taipei City Hospital Renai Branch, Taipei 106, TaiwanDepartment of Internal Medicine, Division of Pulmonary and Critical Care Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, TaiwanImpaired wound healing is an ongoing issue that cancer patients undergoing chemotherapy or radiotherapy face. Our previous study regarding lung-cancer-associated pleural fluid (LCPF) demonstrated its propensity to promote endothelial proliferation, migration, and angiogenesis, which are crucial features during cutaneous wound healing. Therefore, the current study aimed to investigate the effect of pleural fluid on cutaneous wound closure in vitro and in vivo using HaCaT keratinocytes and a full-thickness skin wound model, respectively. Both heart-failure-associated pleural fluid (HFPF) and LCPF were sequentially centrifuged and filtered to obtain a cell-free status. Treatment with HFPF and LCPF homogeneously induced HaCaT proliferation with cell cycle progression, migration, and MMP2 upregulation. Western blotting revealed increased PI3K/Akt phosphorylation and VEGFR2/VEGFA expression in HaCaT cells. When treated with the PI3K inhibitor, LCPF-induced keratinocyte proliferation was attenuated with decreased pS6 levels. By applying the VEGFR2 inhibitor, LCPF-induced keratinocyte proliferation was ameliorated by pS6 and MMP2 downregulation. The effect of LCPF-induced cell junction rearrangement was disrupted by co-treatment with a VEGFR2 inhibitor. Compared with a 0.9% saline dressing, LCPF significantly accelerated wound closure and re-epithelization when used as a dressing material in a full-thickness wound model. Histological analysis revealed increased neo-epidermis thickness and dermis collagen synthesis in the LCPF-treated group. Furthermore, LCPF treatment activated basal keratinocytes at the wound edge with the upregulation of Ki-67, VEGFA, and MMP2. Our preliminaries provided the benefit of wet dressing with pleural fluid to improve cutaneous wound closure through enhanced re-epithelization and disclosed future autologous application in cancer wound treatment.https://www.mdpi.com/2073-4409/11/5/817pleural fluidwound healingkeratinocyteVEGFR2pS6 |
| spellingShingle | Chen-Liang Tsai Chih-Ying Changchien Ying Chen Hsin-Han Chang Wen-Chiuan Tsai Yi-Wen Wang Kai-Chieh Chou Ming-Hsien Chiang Yu-Ling Tsai Hao-Chung Tsai Chieh-Yung Wang Ming-Sheng Shen Li-Ting Cheng Hung-Yi Lin Tse-Bin Yang Chih-Feng Chian Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid Cells pleural fluid wound healing keratinocyte VEGFR2 pS6 |
| title | Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid |
| title_full | Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid |
| title_fullStr | Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid |
| title_full_unstemmed | Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid |
| title_short | Accelerated Wound Healing and Keratinocyte Proliferation through PI3K/Akt/pS6 and VEGFR2 Signaling by Topical Use of Pleural Fluid |
| title_sort | accelerated wound healing and keratinocyte proliferation through pi3k akt ps6 and vegfr2 signaling by topical use of pleural fluid |
| topic | pleural fluid wound healing keratinocyte VEGFR2 pS6 |
| url | https://www.mdpi.com/2073-4409/11/5/817 |
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