Dopamine D2 receptor modulates Wnt expression and control of cell proliferation
Abstract
The Wnt/β-catenin pathway is one of the most conserved signaling pathways across species with essential roles in development, cell proliferation, and disease. Wnt signaling occurs at the protein level and via β-catenin-mediated transcription of target genes. However, little is known about the underlying mechanisms regulating the expression of the key Wnt ligand Wnt3a or the modulation of its activity. Here, we provide evidence that there is significant cross-talk between the dopamine D2 receptor (D2R) and Wnt/β-catenin signaling pathways. Our data suggest that D2R-dependent cross-talk modulates Wnt3a expression via an evolutionarily-conserved TCF/LEF site within the WNT3A promoter. Moreover, D2R signaling also modulates cell proliferation and modifies the pathology in a renal ischemia/reperfusion-injury disease model, via its effects on Wnt/β-catenin signaling. Together, our results suggest that D2R is a transcriptional modulator of Wnt/β-catenin signal transduction with broad implications for health and development of new therapeutics.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Nov 14, 2019
- Source ID
- 10.1038/s41598-019-52528-4
Entities
People
- Allen Ko
- Chaitanya Mokashi
- Fei Han
- Gaosi Xu
- Ines Armando
- John Gildea
- Laureano D Asico
- Megha Kumar
- Pedro A. Jose
- Prasad Konkalmatt
- Robin A. Felder
- Robin E C Lee
- Xiaoxu Zheng
- Yanrong Zhang
- Zachary Freyberg
- Zachary J. Farino
Organizations
- National Heart, Lung, and Blood Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of General Medical Sciences
- National Institute on Drug Abuse
- Pittsburgh Foundation
- United States Department of Defense
- United States Department of Health and Human Services