ArticleCell death & disease2019
TM4SF5-mediated CD44v8-10 splicing variant promotes survival of type II alveolar epithelial cells during idiopathic pulmonary fibrosis.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Ionizing radiation promotes lung injury by inducing ferroptosis-driven senescence in epithelial cells via NCOA4-mediated ferritinophagy.Redox biology · 2026Article
- The role of tetraspanins in organ fibrosis: mechanisms and therapeutic perspectives.Journal of translational medicine · 2025Review
- RNA splicing: Novel star in pulmonary diseases with a treatment perspective.Acta pharmaceutica Sinica. B · 2025Review
- Isoxazole-based molecules restore NK cell immune surveillance in hepatocarcinogenesis by targeting TM4SF5 and SLAMF7 linkage.Signal transduction and targeted therapy · 2025Article
- TNKS1BP1 mediates AECII senescence and radiation induced lung injury through suppressing EEF2 degradation.Respiratory research · 2024Article
- Article
- Liver-originated small extracellular vesicles with TM4SF5 target brown adipose tissue for homeostatic glucose clearance.Journal of extracellular vesicles · 2022Article
- TM4SF5-Mediated Regulation of Hepatocyte Transporters during Metabolic Liver Diseases.International journal of molecular sciences · 2022Review
- Crosstalk between TM4SF5 and GLUT8 regulates fructose metabolism in hepatic steatosis.Molecular metabolism · 2022Article
- TM4SF5-mediated liver malignancy involves NK cell exhaustion-like phenotypes.Cellular and molecular life sciences : CMLS · 2021Article
- TM4SF5 Knockout Protects Mice From Diet-Induced Obesity Partly by Regulating Autophagy in Adipose Tissue.Diabetes · 2021Article
- Amino acid transporters as tetraspanin TM4SF5 binding partners.Experimental & molecular medicine · 2020Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Reactive oxygen species (ROS) regulate cell fate, although signaling molecules that regulate ROS hormesis remain unclear. Here we show that transmembrane 4 L six family member 5 (TM4SF5) in lung epithelial cells induced the alternatively spliced CD44v8-10 variant via an inverse ZEB2/epithelial splicing regulatory proteins (ESRPs) linkage. TM4SF5 formed complexes with the cystine/glutamate antiporter system via TM4SF5- and CD44v8-10-dependent CD98hc plasma-membrane enrichment. Dynamic TM4SF5 binding to CD98hc required CD44v8-10 under ROS-generating inflammatory conditions. TM4SF5 and CD44v8-10 upregulated cystine/glutamate antiporter activity and intracellular glutathione levels, leading to ROS modulation for cell survival. Tm4sf5-null mice exhibited attenuated bleomycin-induced pulmonary fibrosis with lower CD44v8-10 and ESRPs levels than wild-type mice. Primary mouse alveolar epithelial cells (AECs) revealed type II AECs (AECII), but not type I, to adapt the TM4SF5-mediated characteristics, suggesting TM4SF5-mediated AECII survival following AECI injury during idiopathic pulmonary fibrosis (IPF). Thus, the TM4SF5-mediated CD44v8-10 splice variant could be targeted against IPF.
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