Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract
This study aims to investigate the role of integrin α4 (ITGA4) in the inhibition of hepatic stellate cells (HSCs) fibrosis by Periplaneta americana extract (PAE), as well as to explore its molecular mechanisms. In vitro experiments utilized TGFβ-induced LX2 and HSC-T6 cells to examine the anti-fibro...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1517491/full |
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| author | Ying Fang Ye Liu Dingchun Li Yi Miu Kexuan Chen Jv Zhou Lijuan Xie Xinting Chen Jingyan Wu Ying Zhu Lechun Lv Wu Li |
| author_facet | Ying Fang Ye Liu Dingchun Li Yi Miu Kexuan Chen Jv Zhou Lijuan Xie Xinting Chen Jingyan Wu Ying Zhu Lechun Lv Wu Li |
| author_sort | Ying Fang |
| collection | DOAJ |
| description | This study aims to investigate the role of integrin α4 (ITGA4) in the inhibition of hepatic stellate cells (HSCs) fibrosis by Periplaneta americana extract (PAE), as well as to explore its molecular mechanisms. In vitro experiments utilized TGFβ-induced LX2 and HSC-T6 cells to examine the anti-fibrotic effects of PAE, particularly through ITGA4 overexpression, to elucidate its involvement in PAE-mediated inhibition via the PI3K-AKT signaling pathway. Cell viability was assessed using the CCK-8 method, and the IC50 for PAE was determined through statistical analysis. We evaluated cell proliferation using scratch and EDU assays, and migration capabilities using Transwell assays. Molecular mechanisms were investigated through western blot (WB), quantitative PCR (QPCR), and transcriptome analysis. Results indicate that PAE reduces hepatic fibrosis by curbing hepatic stellate cells (HSCs) proliferation, migration, collagen synthesis, inflammatory cytokine production, and epithelial-mesenchymal transition (EMT). Additionally, while PAE suppressed ITGA4’s high expression in activated HSCs, ITGA4 overexpression counteracted PAE’s effects on HSC proliferation, migration, and collagen synthesis. These findings demonstrate that PAE primarily mitigates fibrosis in activated HSCs by inhibiting ITGA4, thus delivering anti-fibrotic effects in the liver. |
| format | Article |
| id | doaj-art-be68941a8af24f93b8f0e80a21ab2951 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-be68941a8af24f93b8f0e80a21ab29512025-08-20T02:46:28ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15174911517491Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extractYing Fang0Ye Liu1Dingchun Li2Yi Miu3Kexuan Chen4Jv Zhou5Lijuan Xie6Xinting Chen7Jingyan Wu8Ying Zhu9Lechun Lv10Wu Li11Department of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaYunnan Key Laboratory of Stem Cell and Regenerative Medicine, School of Rehabilitation, Kunming Medical University, Yunnan, ChinaDepartment of Infectious Disease, The First Affiliated Hospital of Kunming Medical University, Yunnan, ChinaThis study aims to investigate the role of integrin α4 (ITGA4) in the inhibition of hepatic stellate cells (HSCs) fibrosis by Periplaneta americana extract (PAE), as well as to explore its molecular mechanisms. In vitro experiments utilized TGFβ-induced LX2 and HSC-T6 cells to examine the anti-fibrotic effects of PAE, particularly through ITGA4 overexpression, to elucidate its involvement in PAE-mediated inhibition via the PI3K-AKT signaling pathway. Cell viability was assessed using the CCK-8 method, and the IC50 for PAE was determined through statistical analysis. We evaluated cell proliferation using scratch and EDU assays, and migration capabilities using Transwell assays. Molecular mechanisms were investigated through western blot (WB), quantitative PCR (QPCR), and transcriptome analysis. Results indicate that PAE reduces hepatic fibrosis by curbing hepatic stellate cells (HSCs) proliferation, migration, collagen synthesis, inflammatory cytokine production, and epithelial-mesenchymal transition (EMT). Additionally, while PAE suppressed ITGA4’s high expression in activated HSCs, ITGA4 overexpression counteracted PAE’s effects on HSC proliferation, migration, and collagen synthesis. These findings demonstrate that PAE primarily mitigates fibrosis in activated HSCs by inhibiting ITGA4, thus delivering anti-fibrotic effects in the liver.https://www.frontiersin.org/articles/10.3389/fphar.2025.1517491/fullPeriplaneta americana extract (PAE)ITGA4LX2HSC-T6fibrosis |
| spellingShingle | Ying Fang Ye Liu Dingchun Li Yi Miu Kexuan Chen Jv Zhou Lijuan Xie Xinting Chen Jingyan Wu Ying Zhu Lechun Lv Wu Li Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract Frontiers in Pharmacology Periplaneta americana extract (PAE) ITGA4 LX2 HSC-T6 fibrosis |
| title | Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract |
| title_full | Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract |
| title_fullStr | Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract |
| title_full_unstemmed | Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract |
| title_short | Role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by Periplaneta americana extract |
| title_sort | role of integrin α4 in the inhibition of fibrosis in activated hepatic stellate cells by periplaneta americana extract |
| topic | Periplaneta americana extract (PAE) ITGA4 LX2 HSC-T6 fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1517491/full |
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