An article titled, “Neuroendocrine cells orchestrate regeneration through Desert hedgehog signaling,” was published in Cell by authors William Kong, Wan-Jin Lu, Megha Dubey, Rahul K. Suryawanshi, Sivakamasundari Vijayakumar, Youngtae Jeong, Saurabh Gombar, Maximilian Diehn, Kunyoo Shin, Melanie Ott, Yueh-hsiu Chien, Kavita Y. Sarin, Tushar J. Desai, and Philip A. Beachy, affiliated with Atropos Health, Stanford University School of Medicine, and University of California, San Francisco.
Key Highlights:
- Desert hedgehog (Dhh) is expressed in airway and pancreatic islet neuroendocrine cells
- Dhh elicits protective/regenerative response via epithelial-mesenchymal feedback (EMF)
- This finding demonstrates the potential for protective/therapeutic utility in chemical or infectious airway injury and in diabetes.
Short Summary:
Understanding the mechanisms underlying mammalian regeneration may enable development of novel regenerative therapies. This research presents 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 SO2 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 SO2 and influenza infection, with potential protective/therapeutic utility in chemical or infectious airway injury and in diabetes.
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