Journal article
Dopamine receptor signaling regulates fibrotic activation of retinal pigmented epithelial cells
American Journal of Physiology: Cell Physiology, Vol.323(1), pp.C116-C124
07/11/2022
DOI: 10.1152/ajpcell.00468.2021
Abstract
Retinal pigmented epithelial (RPE) cells play an important role in retinal fibrotic diseases such as proliferative vitreoretinopathy (PVR). The purpose of this study was to elucidate the involvement of dopamine receptor signaling in regulating the fibrotic activation of RPE cells. Dopamine receptor expression, the effect of dopamine on fibrotic activity, and dopamine production were measured in the human RPE cell line ARPE-19. The fibrotic activation of RPE cells was evaluated in response to treatments with selective dopamine receptor agonists and antagonists by measuring gene expression, migration, proliferation, and fibronectin deposition. DRD2 and DRD5 are the dominant dopaminergic receptors expressed in ARPE-19 cells and TGF-beta stimulation enhances the autocrine release of dopamine, which we show further exasperates fibrotic activation. Finally, treatment with D2 dopamine receptor antagonists or D5 dopamine receptor agonists inhibits profibrotic gene expression, migration, proliferation, and fibronectin deposition and thus may serve as effective mechanisms for treating retinal fibrosis including PVR.
Details
- Title: Subtitle
- Dopamine receptor signaling regulates fibrotic activation of retinal pigmented epithelial cells
- Creators
- Ashley Y. Gao - Mayo ClinicPatrick A. Link - Mayo ClinicSophie J. Bakri - Mayo ClinicAndrew J. Haak - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- American Journal of Physiology: Cell Physiology, Vol.323(1), pp.C116-C124
- DOI
- 10.1152/ajpcell.00468.2021
- ISSN
- 0363-6143
- eISSN
- 1522-1563
- Publisher
- Amer Physiological Soc
- Number of pages
- 9
- Grant note
- Pulmonary Fibrosis Foundation Scholars Award 1R61HL161804-01 / NIH NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) Boehringer Ingelheim Discovery Award in Interstitial Lung Disease; Boehringer Ingelheim Brewer Family Mayo Clinic Career Development Award 5T32HL105355-10; F32HL158018; L30HL159704; R01HL153026 / National Institutes of Health (NIH) NHLBI; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) American Lung Association Catalyst Award
- Language
- English
- Date published
- 07/11/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Craniofacial Anomalies Research Center
- Record Identifier
- 9984948141802771
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