Association of DPP4 with esophageal stricture progression and the Hippo‐YAP pathway
5 affiliations
- 1Department of Critical Care Medicine Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University Nanjing China
- 2Department of Gastroenterology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu Province China
- 3Department of Gynecology The First Affiliated Hospital of Nanjing Medical University Nanjing Jiangsu Province China
- 4Department of Gastroenterology The Affiliated Changzhou Second People's Hospital of Nanjing Medical University, Changzhou Second People's Hospital, Changzhou Medical Center, Nanjing Medical University Changzhou China
- 5Department of Gastroenterology The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University Changzhou China
Abstract
Background: Esophageal stricture (ES), a common complication after endoscopic submucosal dissection (ESD), is the consequence of excessive fibrosis and scar formation. The fibroblast‐to‐myofibroblast differentiation is a key characteristic in the pathogenesis of ES, but the molecular basis remains poorly understood.
Methods: According to the human transcriptome sequencing analysis, which utilized different expression gene analysis and weighted gene co‐expression network analysis, the potential gene associated with ES was explored. Furthermore, we utilized the rat model of ES and the temporal progression of ES after drug treatment to elucidate the role of DPP4 in ES. Subsequently, we identified a significant association between DPP4 and the progression of ES. Finally, we validated our conclusions through experiments on Bama pigs.
Results: DPP4 expression was consistently elevated in both human ES tissues and the rat ES model. Upon inhibition of DPP4, the proliferative activity of ES primary cells and the expression of fibrosis‐related genes were markedly suppressed. In rats, treatment with a DPP4 inhibitor significantly alleviated ES, which was accompanied by a significant reduction in collagen content and downregulation of fibrosis‐related targets. These effects were observed in conjunction with changes in the Hippo‐YAP pathway, although the data primarily support a parallel association rather than a hierarchical regulatory relationship between DPP4 and this pathway.
Conclusions: Our findings suggest that DPP4 may contribute to the remodeling of the regenerative microenvironment in ES, with its expression and function occurring in parallel with alterations in the Hippo‐YAP pathway. Direct mechanistic evidence establishing a linear upstream–downstream relationship between DPP4 and Hippo‐YAP signaling remains to be further elucidated.
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BibTeX
@article{wu2026association,
title = {{Association of DPP4 with esophageal stricture progression and the Hippo‐YAP pathway}},
author = {Rui Wu and Chen Wang and Hui‐Min Tao and Jin Huang and Wei‐Qin Li and Zhi‐Ning Fan},
journal = {Animal Models and Experimental Medicine},
year = {2026},
month = sep,
doi = {10.1002/ame2.70239},
url = {https://doi.org/10.1002/ame2.70239},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Association of DPP4 with esophageal stricture progression and the Hippo‐YAP pathway
AU - Rui Wu
AU - Chen Wang
AU - Hui‐Min Tao
AU - Jin Huang
AU - Wei‐Qin Li
AU - Zhi‐Ning Fan
PY - 2026
DA - 2026/09/01
JO - Animal Models and Experimental Medicine
DO - 10.1002/ame2.70239
UR - https://doi.org/10.1002/ame2.70239
AB - Background: Esophageal stricture (ES), a common complication after endoscopic submucosal dissection (ESD), is the consequence of excessive fibrosis and scar formation. The fibroblast‐to‐myofibroblast differentiation is a key characteristic in the pathogenesis of ES, but the molecular basis remains poorly understood. Methods: According to the human transcriptome sequencing analysis, which utilized different expression gene analysis and weighted gene co‐expression network analysis, the potential gene associated with ES was explored. Furthermore, we utilized the rat model of ES and the temporal progression of ES after drug treatment to elucidate the role of DPP4 in ES. Subsequently, we identified a significant association between DPP4 and the progression of ES. Finally, we validated our conclusions through experiments on Bama pigs. Results: DPP4 expression was consistently elevated in both human ES tissues and the rat ES model. Upon inhibition of DPP4, the proliferative activity of ES primary cells and the expression of fibrosis‐related genes were markedly suppressed. In rats, treatment with a DPP4 inhibitor significantly alleviated ES, which was accompanied by a significant reduction in collagen content and downregulation of fibrosis‐related targets. These effects were observed in conjunction with changes in the Hippo‐YAP pathway, although the data primarily support a parallel association rather than a hierarchical regulatory relationship between DPP4 and this pathway. Conclusions: Our findings suggest that DPP4 may contribute to the remodeling of the regenerative microenvironment in ES, with its expression and function occurring in parallel with alterations in the Hippo‐YAP pathway. Direct mechanistic evidence establishing a linear upstream–downstream relationship between DPP4 and Hippo‐YAP signaling remains to be further elucidated.
SN - 2096-5451
SN - 2576-2095
ER -