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National Institute of Environmental Health Sciences

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Publication Detail

Title: Cyp1b1-deficient retinal astrocytes are more proliferative and migratory and are protected from oxidative stress and inflammation.

Authors: Falero-Perez, Juliana; Sorenson, Christine M; Sheibani, Nader

Published In Am J Physiol Cell Physiol, (2019 Jun 01)

Abstract: Astrocytes (ACs) are the most abundant cells in the central nervous system. Retinal ACs play an important role in maintaining the integrity of retinal neurovascular function, and their dysfunction contributes to the pathogenesis of various eye diseases including diabetic retinopathy. Cytochrome P450 1B1 (CYP1B1) expression in the neurovascular structures of the central nervous system including ACs has been reported. We previously showed that CYP1B1 expression is a key regulator of redox homeostasis in retinal vascular cells. Its deficiency in mice resulted in increased oxidative stress and attenuation of angiogenesis in vivo and proangiogenic activity of retinal vascular cells in vitro. Here, using retinal ACs prepared from wild-type (Cyp1b1+/+) and Cyp1b1-deficient (Cyp1b1-/-) mice, we determined the impact of Cyp1b1 expression on retinal AC function. We showed that Cyp1b1-/- retinal ACs were more proliferative and migratory. These cells also produced increased amounts of fibronectin and its receptors, αvβ3- and α5β1-integrin. These results were consistent with the increased adhesive properties of Cyp1b1-/- ACs and their lack of ability to form a network in Matrigel. This was reversed by reexpression of Cyp1b1 in Cyp1b1-/- ACs. Although no significant changes were observed in Akt/SRC/MAPK signaling pathways, production of inflammatory mediators bone morphogenetic protein-7 (BMP-7) and monocyte chemoattractant protein-1 (MCP-1) was decreased in Cyp1b1-/- ACs. Cyp1b1-/- ACs also showed increased levels of connexin 43 phosphorylation and cluster of differentiation 38 expression when challenged with H2O2. These results are consistent with increased proliferation and diminished oxidative stress in Cyp1b1-/- cells. Thus, Cyp1b1 expression in ACs plays an important role in retinal neurovascular homeostasis.

PubMed ID: 30892936 Exiting the NIEHS site

MeSH Terms: Animals; Astrocytes/drug effects; Astrocytes/metabolism*; Cell Movement/drug effects; Cell Movement/physiology; Cell Proliferation/drug effects; Cell Proliferation/physiology*; Cells, Cultured; Cytochrome P-450 CYP1B1/biosynthesis*; Hydrogen Peroxide/toxicity; Inflammation Mediators/antagonists & inhibitors; Inflammation Mediators/metabolism*; Inflammation/metabolism; Inflammation/prevention & control; Mice; Mice, Inbred C57BL; Mice, Knockout; Oxidative Stress/drug effects; Oxidative Stress/physiology*; Retinal Vessels/cytology; Retinal Vessels/drug effects; Retinal Vessels/metabolism*

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