ORIGINAL PAPER
KLF7 enhances the inflammatory response in LPS-induced alveolar epithelial cells via activating the LIMK1/SRPK1 pathway
1
Respiratory and Critical Care Discipline Zone 1, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, Hunan Province, China
2
Respiratory and Critical Care Discipline Zone 3, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, Hunan Province, China
3
Intensive Care Medicine Department, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou 412007, Hunan Province, China
These authors had equal contribution to this work
Submission date: 2024-12-18
Final revision date: 2025-02-27
Acceptance date: 2025-03-15
Online publication date: 2025-10-06
Publication date: 2025-10-06
KEYWORDS
ABSTRACT
Introduction:
Krüppel-like factor 7 (KLF7) exhibits pro-inflammatory properties in numerous diseases, but its precise function in acute lung injury (ALI) remains ambiguous. This study aimed to elucidate the molecular mechanism of KLF7 in type II alveolar epithelial cells under ALI conditions.
Material and methods:
Cell Counting Kit-8 (CCK-8) assay and flow cytometry were employed to assess cell viability and apoptosis. The binding of KLF7 and LIM kinase 1 (LIMK1) promoter was tested by ChIP and dual-luciferase assays. GST pull-down and Co-IP assays verified the interaction between LIMK1 and serine arginine protein kinase 1 (SRPK1). Levels of inflammatory cytokines were measured by ELISA test. Western blot and quantitative real-time PCR were applied to assess the expression of related factors.
Results:
KLF7 was upregulated in LPS-treated alveolar epithelial cells, and its knockdown attenuated cell apoptosis and inflammation by promoting cell viability and decreasing tumor necrosis factor (TNF-), interleukin 1 (IL-1) and interleukin 6 (IL-6) levels. LIMK1 was transcriptionally activated by KLF7. The suppression of cell apoptosis and inflammation caused by KLF7 depletion was counteracted by LIMK1 overexpression. LIMK1 bound to SRPK1 protein to promote its phosphorylation. SRPK1 inhibition mitigated the effects of LIMK1 overexpression combined with KLF7 knockdown in LPS-treated alveolar epithelial cells.
Conclusions:
KLF7 intensified the inflammatory response of alveolar epithelial cells under ALI conditions by modulating the LIMK1/SRPK1 axis.
Krüppel-like factor 7 (KLF7) exhibits pro-inflammatory properties in numerous diseases, but its precise function in acute lung injury (ALI) remains ambiguous. This study aimed to elucidate the molecular mechanism of KLF7 in type II alveolar epithelial cells under ALI conditions.
Material and methods:
Cell Counting Kit-8 (CCK-8) assay and flow cytometry were employed to assess cell viability and apoptosis. The binding of KLF7 and LIM kinase 1 (LIMK1) promoter was tested by ChIP and dual-luciferase assays. GST pull-down and Co-IP assays verified the interaction between LIMK1 and serine arginine protein kinase 1 (SRPK1). Levels of inflammatory cytokines were measured by ELISA test. Western blot and quantitative real-time PCR were applied to assess the expression of related factors.
Results:
KLF7 was upregulated in LPS-treated alveolar epithelial cells, and its knockdown attenuated cell apoptosis and inflammation by promoting cell viability and decreasing tumor necrosis factor (TNF-), interleukin 1 (IL-1) and interleukin 6 (IL-6) levels. LIMK1 was transcriptionally activated by KLF7. The suppression of cell apoptosis and inflammation caused by KLF7 depletion was counteracted by LIMK1 overexpression. LIMK1 bound to SRPK1 protein to promote its phosphorylation. SRPK1 inhibition mitigated the effects of LIMK1 overexpression combined with KLF7 knockdown in LPS-treated alveolar epithelial cells.
Conclusions:
KLF7 intensified the inflammatory response of alveolar epithelial cells under ALI conditions by modulating the LIMK1/SRPK1 axis.
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| eISSN: | 1644-4124 |
| ISSN: | 1426-3912 |
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