Neuroendocrine cells orchestrate regeneration through Desert hedgehog signaling.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40494346.
- Also identified by DOI 10.1016/j.cell.2025.05.012 and PMC identifier 12232213.
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Abstract
Understanding the mechanisms underlying mammalian regeneration may enable development of novel regenerative therapies. We present a mechanism wherein Desert hedgehog (Dhh), secreted from epithelial neuroendocrine cells, elicits a regenerative/protective response from mesenchymal cells. In mammalian airway, this mesenchymal response strikingly amplifies the initial signal from rare neuroendocrine cells to activate the entire tissue for survival and regeneration upon injury from SO<sub>2</sub> gas inhalation or following influenza or SARS-CoV-2 infection. Similar epithelial-mesenchymal feedback (EMF) signaling directed by Dhh from neuroendocrine β cells likewise protects mouse pancreatic islets from streptozotocin (STZ) injury. A role for EMF signaling in human pancreatic islets is suggested by higher incidence of diabetes in patients treated with Hedgehog pathway inhibitors. Remarkably, EMF augmentation by small-molecule Hedgehog pathway agonism protects against STZ injury of pancreatic β cells and shields against airway injury from SO<sub>2</sub> and influenza infection, with potential protective/therapeutic utility in chemical or infectious airway injury and in diabetes.
Medical subject headings
- Hedgehog Proteins
- Signal Transduction
- Regeneration
- Neuroendocrine Cells