Related Experiment Videos
Cellular retinoic acid bioavailability in various pathologies and its therapeutic implication.
1Department of Pathology, Sapporo Medical University School of Medicine, Sapporo, Japan.
Pathology International
|April 20, 2017
Summary
Retinoic acid (RA) depletion promotes cancer by affecting cellular RA bioavailability. Restoring RA levels in retinal astrocytes and epithelial cells can prevent vascular leakiness and barrier loss in diseases like diabetic retinopathy and colitis.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Retinoic acid (RA), a vitamin A metabolite, is crucial for cell signaling.
- Cellular RA bioavailability, not serum levels, dictates RA's biological effects.
- Stellate cells store vitamin A and regulate cellular RA bioavailability.
Purpose of the Study:
- To investigate the role of RA depletion in carcinogenesis via CYP26A1.
- To explore the function of retinal astrocytes in vascular integrity.
- To assess RA's therapeutic potential in diseases with compromised barriers.
Main Methods:
- Investigated the effect of CYP26A1 expression on carcinogenesis.
- Examined the paracrine regulation of endothelial integrity by retinal astrocytes.
- Assessed RA's impact on vascular leakiness in diabetic retinopathy models.
- Evaluated RA's effect on epithelial barrier integrity in experimental colitis.
Main Results:
- CYP26A1-mediated RA depletion promotes carcinogenesis, identifying it as a candidate oncogene.
- Retinal astrocytes regulate endothelial integrity, and RA normalizes compromised astrocytes in diabetes.
- RA suppresses vascular leakiness in diabetic retinopathy and attenuates epithelial barrier loss in colitis.
Conclusions:
- Cellular RA bioavailability is critical in regulating cellular functions and disease pathogenesis.
- Targeting the stellate cell system and enhancing cellular RA bioavailability offers a potential therapeutic strategy for RA-insufficiency diseases.