SOX11 and FAK participate in the stretch‑induced mechanical injury to alveolar type 2 epithelial cells

Fang,Mingxing; Xu,Tieling; Fan,Shujuan; Liu,Na; Li,Luping; Gao,Junxia; Li,Wenbin

doi:10.3892/ijmm.2020.4795

SOX11 and FAK participate in the stretch‑induced mechanical injury to alveolar type 2 epithelial cells

Authors:
- Mingxing Fang
- Tieling Xu
- Shujuan Fan
- Na Liu
- Luping Li
- Junxia Gao
- Wenbin Li
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Affiliations: Department of Pathophysiology, Neuroscience Research Center, Hebei Medical University, Shijiazhuang, Hebei 050017, P.R. China, Department of Emergency, Hebei General Hospital, Shijiazhuang, Hebei 050000, P.R. China, Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China, Experimental Center, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei 050051, P.R. China
Published online on: November 20, 2020 https://doi.org/10.3892/ijmm.2020.4795
Pages: 361-373
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to explore the potential role of SOX11 in the stretch‑induced mechanical injury to alveolar type 2 epithelial (AT2) cells. A cell stretch (CS) test was used to induce mechanical injury to primary cultured AT2 cells. Wound healing, adhesion, cell viability assays and flow cytometry were performed to evaluate the migration, adhesion, viability and apoptosis of AT2 cells. Changes in the invasive ability of AT2 cells were detected using a Transwell invasion assay. To further explore the underlying molecular mechanisms, reverse transcription‑quantitative PCR and western blot analysis were used to assess the expression levels of SOX11, FAK, Akt, caspase‑3/8, p65 and matrix metalloproteinase (MMP)7. Co‑immunoprecipitation (Co‑IP) and luciferase reporter assays were used to detect the interaction between SOX11 and FAK. CS reduced the invasion, migration and adhesion, and increased the apoptosis of AT2 cells. It also resulted in the downregulation of SOX11 and FAK expression in AT2 cells. The overexpression of SOX11 reversed these changes, whereas the knockdown of SOX11 aggravated the deterioration of the aforementioned biological behaviors and the apoptosis of the AT2 cells following CS. The overexpression of SOX11 upregulated the FAK and Akt expression levels, and downregulated caspase‑3/8 expression, whereas the silencing of SOX11 reversed these changes following CS. Furthermore, the effects of SOX11 overexpression were inhibited by FAK antagonism. The results of Co‑IP demonstrated that SOX11 and FAK were bound together, and that the expression of FAK was significantly increased in the SOX11 overexpression group. Luciferase assays revealed that the luciferase activity and the mRNA expression of FAK were significantly increased following transfection with pcDNA SOX11 and pGL3 FAK promoter. Co‑IP and luciferase assays revealed that SOX11 directly regulated the expression of FAK. On the whole, the present study demonstrates that the downregulated expression of SOX11 and FAK are involved in the stretch‑induced mechanical injury to AT2 cells. The overexpression of SOX11 significantly alleviates AT2 cell injury through the upregulation of FAK and Akt, and the inhibition of apoptosis. These findings suggest that the activation of SOX11 and FAK may be potential preventive and therapeutic options for ventilator‑induced lung injury.

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