ArticleCell death & disease2021
TSSK4 upregulation in alveolar epithelial type-II cells facilitates pulmonary fibrosis through HSP90-AKT signaling restriction and AT-II apoptosis.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- Recent advances in pulmonary fibrosis: from lung surfactant to the immune connection.Respiratory research · 2026Review
- Network pharmacology and molecular docking reveal mechanisms of amiodarone-induced pulmonary fibrosis.Scientific reports · 2026Article
- MiR-18a-5p serves as a risk factor in perioperative respiratory adverse events in children under general anesthesia.Perioperative medicine (London, England) · 2025Article
- Pulmonary fibrosis: from mechanisms to therapies.Journal of translational medicine · 2025Review
- Targeting Hsp90α to inhibit HMGB1-mediated renal inflammation and fibrosis.Cell proliferation · 2025Article
- YAP as a potential therapeutic target for myofibroblast formation in asthma.Respiratory research · 2025Article
- Systems Biology of Recombinant 2G12 and 353/11 mAb Production in CHO-K1 Cell Lines at Phosphoproteome Level.Proteomes · 2025Article
- PLAC8 attenuates pulmonary fibrosis and inhibits apoptosis of alveolar epithelial cells via facilitating autophagy.Communications biology · 2025Article
- Phenolic Glycoside Monomer fromCurrent medicinal chemistry · 2025Article
- The role of heat shock protein 90 in idiopathic pulmonary fibrosis: state of the art.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Biomechanical Properties and Cellular Responses in Pulmonary Fibrosis.Bioengineering (Basel, Switzerland) · 2024Review
- Expression and significance of serum KL-6 in patients with acute respiratory distress syndrome.Journal of thoracic disease · 2023Article
- Fraxetin alleviates BLM-induced idiopathic pulmonary fibrosis by inhibiting NCOA4-mediated epithelial cell ferroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- HUB genes transcriptionally regulate lipid metabolism in alveolar type II cells under LPS stimulation.Heliyon · 2023Article
- Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers.Antioxidants (Basel, Switzerland) · 2023Review
- Potential of resveratrol in the treatment of interstitial lung disease.Frontiers in pharmacology · 2023Review
- The Role of Pulmonary Surfactant Phospholipids in Fibrotic Lung Diseases.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Alveolar epithelial injury is one of the important pathological changes in idiopathic pulmonary interstitial fibrosis (IPF), but the regulatory mechanism remains unclear. Here, we reported that alveolar epithelial type-II cells (AT II) play important roles in pathological process of pulmonary fibrosis. Through iTRAQ (isobaric tagging for relative and absolute quantification) quantitative proteomics, TSSK4 was identified to be upregulated in bleomycin-induced fibrotic mice model, which was further confirmed in clinical IPF patients' tissue specimens. TSSK4 is a germ-related protein, but its expression in other tissues and the association with other diseases are not reported. Immunofluorescence staining showed that TSSK4 selectively expressed in AT-II cells, which are essential for inflammation-induced AT-II loss during fibrosis. Luciferase assay and other molecular biological experiments proved that TSSK4 expression is regulated by TNF-α-mediated NF-κB signaling. The TSSK4 kinase activity is found to be closely related to the function of HSP90-AKT pathway that TSSK4 can phosphorylate its substrate HSP90β on serine 255, to inhibit the ATPase activity of HSP90β and reduce its molecular chaperone function on AKT. Under this condition, kinase activity of AKT is diminished to interfere its survival function, subsequently facilitating AT-II cellular apoptosis through the mitochondrial death machinery. Our findings highlight the importance of TSSK4 in regulating pulmonary fibrosis by facilitating AT-II loss through HSP90-AKT signaling, all of which suggest TSSK4 and the regulating mechanism as attractive targets for the clinical intervention of pulmonary injury and fibrosis.
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