Researchers at Baylor College of Medicine and collaborating institutions took a closer look at how the gastrointestinal tissue repairs itself. They reveal in the Proceedings of the National Academy of Sciences key players and their connections in the repair process and suggest the possibility that they also may contribute to the repair of other types of tissues.
“In the current study, we focused on the repair process followed by cells in the mouse stomach called chief cells, which specialize in secreting digestive enzymes,” said corresponding author Dr. Jason Mills , Herman Brown Endowed Professor of Medicine Gastroenterology and Hepatology at Baylor. “When tissue is injured, chief cells revert to a regenerative state – they reacquire stem cell properties that allow them to reproduce and regenerate damaged areas via a process called paligenosis.”
Chief cells transform into repair cells through three stages. First, chief cells recycle or self-digest many of their cellular components. “The cells are trying to downsize, clearing space and removing previous structures,” Mills said.
The second stage involves changes in gene expression, activating genes that allow the cells to become more like repair cells. The third and final stage is cell proliferation, when the cells divide to regenerate damaged tissue.
“We wanted to understand what triggers and controls these stages,” said first author Dr. Yongji Zeng , postdoctoral associate of medicine – gastroenterology at Baylor. “We discovered that when damaged chief cells go through the first stage of massive self-digestion of their cellular components, an enzyme called STK38 is destroyed. STK38 normally acts like a brake on another protein called YAP1, rendering it inactive. But in the absence of STK38, YAP1 is activated, carrying on its role of inducing the expression of genes that mediate the return of chief cells to a stem cell state (stage two), and then proliferation (stage three). We are excited because STK38 had not been previously linked to YAP1 regulation in paligenosis and tissue regeneration.”
“Although the main experiments were conducted in stomach chief cells, we observed that injury to other tissues, such as pancreatic acinar cells (which regenerate after pancreatitis) and human gastric tissues showing early cancer related changes, also triggered destruction of STK38 by self-digestion and consequent YAP1 activation,” Mills said. “This suggests that the STK38–YAP1 switch may be a general mechanism for mature cells to regain regenerative properties – not just in the stomach, but across many organs. Having a better understanding of paligenosis can lead to improved strategies for tissue regeneration and potentially cancer.”
Authors Yang-Zhe Huang, Raymond Ho and Steven J. Bark are affiliated with Baylor College of Medicine. Qing Kay Li is with Johns Hopkins Medical Institutions and Spencer G. Willet with Washington University School of Medicine.
For a complete list of the sources of financial support for this project, see the publication.
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Proceedings of the National Academy of Sciences
Experimental study
Animal tissue samples
Regulation of STK38 by autophagy governs YAP1 activity during paligenosis
30-Mar-2026