Retinal astrocytes transcriptome reveals Cyp1b1 regulates the expression of genes involved in cell adhesion and migration

Abstract

Astrocytes (AC) are the most abundant cells in the central nervous system. In the retina, astrocytes play important roles in the development and integrity of the retinal neurovasculature. Astrocytes dysfunction contributes to pathogenesis of a variety of neurovascular diseases including diabetic retinopathy. Recent studies have demonstrated the expression of Cyp1b1 in the neurovascular cells of the central nervous system including AC. We recently showed retinal AC constitutively express Cyp1b1, and global Cyp1b1-deficiency (Cyp1b1-/-) attenuates retinal ischemia-mediated neovascularization in vivo and the pro-angiogenic activity of retinal vascular cells in vitro. We also demonstrated that Cyp1b1 expression is a key regulator of retinal AC function. However, the underlying mechanisms involved need further investigation. Here we determined changes in the transcriptome profiles of Cyp1b1+/+ and Cyp1b1-/retinal AC by RNA sequencing. We identified 585 differentially expressed genes, whose pathway enrichment analysis revealed the most significant pathways impacted in Cyp1b1-/-AC. These genes included those of axon guidance, extracellular matrix proteins and their receptors, cancer, cell adhesion molecules, TGF-β signaling, and the focal adhesion modulation. The expression of a selected set of differentially expressed genes was confirmed by RT-qPCR analysis. To our knowledge, this is the first report of RNAseq investigation of the retinal AC transcriptome and the molecular pathways impacted by Cyp1b1 expression. These results demonstrated an important role for Cyp1b1 expression in the regulation of various retinal AC functions, which are important in neurovascular development and integrity.

Identification and Integrate Analysis of Key Biomarkers for Diagnosis and Prognosis of Non-Small Cell Lung Cancer Based on Bioinformatics Analysis

“…In normal and tumor cells, mitotic nuclear division, cell cycle, and meiotic division of oocytes are known to be important cellular processes, 28 and key tumor-related genes usually modulate tumor progression by regulating these cellular processes. 29 Furthermore, some studies have shown that cell adhesion molecules play crucial roles in tumor development, 30 consistent with our current results. Thus, although the specific mechanisms of disease progression are still not clearly defined, the signaling pathways identified above were confirmed to be related to NSCLC.…”

Polymorphisms in CYP1B1 gene and the risk of suffering Primary Open-Angle Glaucoma: Systematic review and meta-analysis

“…1,26 Our hypothesis could therefore be that given SNPs in CYP1B1 gene may modify the synthesis of Cyp1b1 enzyme, which is crucial in reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. 10,34,35 It had been reported that a decreased activity of the Cyp1b1 enzyme could be associated with an increment of the oxidative stress 36 affecting the protein stability or corrupting collagen disposition in some body tissues like trabecular meshwork's. 8 In addition, CYP1B1 gene SNP also could modify metabolism of the retinol, stradiol and other complex molecules such as polycyclic aromatic hydrocarbons metabolism.…”

Investigating the Mechanisms of Pollen Typhae in the Treatment of Diabetic Retinopathy Based on Network Pharmacology and Molecular Docking

“…Focal adhesion signaling pathway was important for maintaining the integrity of retinal vascular structure and function [51,52]. According to the study results, those genes enriched in focal adhesion signaling pathway were considerably upregulated [53][54][55]. Moreover, proteomic bioinformatic analysis in DR indicated that DR development was closely related to focal adhesion and PI3K-Akt signaling pathway [56].…”