ArticleClinical cancer research : an official journal of the American Association for Cancer Research2014
Transient activation of hedgehog pathway rescued irradiation-induced hyposalivation by preserving salivary stem/progenitor cells and parasympathetic innervation.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 47 citations in OpenAlex.
- Intragland Expression of the Shh Gene Alleviates Irradiation-Induced Salivary Gland Injury through Microvessel Protection and the Regulation of Oxidative Stress.Antioxidants (Basel, Switzerland) · 2024Article
- A Salivary Gland Resident Macrophage Subset Regulating Radiation Responses.Journal of dental research · 2023Article
- Identifying Fibrogenic Cells Following Salivary Gland Obstructive Injury.bioRxiv : the preprint server for biology · 2023Article
- Gene Therapeutic Delivery to the Salivary Glands.Advances in experimental medicine and biology · 2023Article
- Identifying fibrogenic cells following salivary gland obstructive injury.Frontiers in cell and developmental biology · 2023Article
- Role of Transient Receptor Potential Vanilloid 1 in Sonic Hedgehog-Dependent Taste Bud Differentiation.Life (Basel, Switzerland) · 2022Article
- Sphingosine-1-Phosphate Alleviates Irradiation Induced Salivary Gland Hypofunction through Preserving Endothelial Cells and Resident Macrophages.Antioxidants (Basel, Switzerland) · 2022Article
- Salivary gland function, development, and regeneration.Physiological reviews · 2022Review
- Transient Activation of Hedgehog Signaling Inhibits Cellular Senescence and Inflammation in Radiated Swine Salivary Glands through Preserving Resident Macrophages.International journal of molecular sciences · 2021Article
- Mechanism, Prevention, and Treatment of Radiation-Induced Salivary Gland Injury Related to Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Review
- Identification of Molecules Responsible for Therapeutic Effects of Extracellular Vesicles Produced from iPSC-Derived MSCs on Sjo¨gren's Syndrome.Aging and disease · 2021Article
- The Radiation-Induced Regenerative Response of Adult Tissue-Specific Stem Cells: Models and Signaling Pathways.Cancers · 2021Review
- Advances on mechanism and treatment of salivary gland in radiation injury.Hua xi kou qiang yi xue za zhi = Huaxi kouqiang yixue zazhi = West China journal of stomatology · 2021Article
- Radiation-Induced Salivary Gland Dysfunction: Mechanisms, Therapeutics and Future Directions.Journal of clinical medicine · 2020Review
- Transient Activation of the Hedgehog-Gli Pathway Rescues Radiotherapy-Induced Dry Mouth via Recovering Salivary Gland Resident Macrophages.Cancer research · 2020Article
- Alpha-Lipoic Acid Ameliorates Radiation-Induced Salivary Gland Injury by Preserving Parasympathetic Innervation in Rats.International journal of molecular sciences · 2020Article
- Epithelial Cell Lineage and Signaling in Murine Salivary Glands.Journal of dental research · 2019Review
- Review
- Comparing human and mouse salivary glands: A practice guide for salivary researchers.Oral diseases · 2019Review
- Delivery of Sonic Hedgehog Gene Repressed Irradiation-induced Cellular Senescence in Salivary Glands by Promoting DNA Repair and Reducing Oxidative Stress.Theranostics · 2018Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
purposeTo examine the effects and mechanisms of transient activation of the Hedgehog pathway on rescuing radiotherapy-induced hyposalivation in survivors of head and neck cancer. EXPERIMENTAL
designMouse salivary glands and cultured human salivary epithelial cells were irradiated by a single 15-Gy dose. The Hedgehog pathway was transiently activated in mouse salivary glands, by briefly overexpressing the Sonic hedgehog (Shh) transgene or administrating smoothened agonist, and in human salivary epithelial cells, by infecting with adenovirus encoding Gli1. The activity of Hedgehog signaling was examined by the expression of the Ptch1-lacZ reporter and endogenous Hedgehog target genes. The salivary flow rate was measured following pilocarpine stimulation. Salivary stem/progenitor cells (SSPC), parasympathetic innervation, and expression of related genes were examined by flow cytometry, salisphere assay, immunohistochemistry, quantitative reverse transcription PCR, Western blotting, and ELISA.
resultsIrradiation does not activate Hedgehog signaling in mouse salivary glands. Transient Shh overexpression activated the Hedgehog pathway in ductal epithelia and, after irradiation, rescued salivary function in male mice, which is related with preservation of functional SSPCs and parasympathetic innervation. The preservation of SSPCs was likely mediated by the rescue of signaling activities of the Bmi1 and Chrm1-HB-EGF pathways. The preservation of parasympathetic innervation was associated with the rescue of the expression of neurotrophic factors such as Bdnf and Nrtn. The expression of genes related with maintenance of SSPCs and parasympathetic innervation in female salivary glands and cultured human salivary epithelial cells was similarly affected by irradiation and transient Hedgehog activation.
conclusionsThese findings suggest that transient activation of the Hedgehog pathway has the potential to restore salivary gland function after irradiation-induced dysfunction.
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Registered trials
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