+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Transcriptional regulation of VEGFA by the endoplasmic reticulum stress transducer OASIS in ARPE-19 cells



Transcriptional regulation of VEGFA by the endoplasmic reticulum stress transducer OASIS in ARPE-19 cells



Plos One 8(1): E55155



Vascular endothelial growth factor-A (VEGFA) is the main mediator of angiogenesis. Angiogenesis plays important roles not only in many physiological processes, but also in the pathophysiology of many diseases. VEGFA is one of the therapeutic targets of treatment for ocular diseases with neovascularization. Therefore, elucidation of the regulatory mechanisms for VEGFA expression is important for the development of pharmaceutical drugs. Recent studies have demonstrated that the unfolded protein response is involved in the transcriptional regulation of VEGFA. However, the precise regulation of VEGFA in the human retina is not fully understood. When human retinal pigment epithelial cells, ARPE-19, were exposed to endoplasmic reticulum stressors, VEGFA mRNA was significantly upregulated. The unfolded protein response-related transcription factors XBP1, ATF4, ATF6, and OASIS were expressed in ARPE-19 cells. To determine which transcription factors preferentially contribute to the induction of VEGFA expression after endoplasmic reticulum stress, we carried out reporter assays using an approximately 6-kbp 5'-upstream region of the human VEGFA gene. Among these transcription factors, OASIS acted most effectively on the VEGFA promoter in ARPE-19 cells. Based on data obtained for certain deleted and mutated reporter constructs, we determined that OASIS promoted VEGFA expression by acting on a cyclic AMP-responsive element-like site located at around -500 bp relative to the VEGFA transcription start site. Furthermore, we confirmed that OASIS directly bound to the promoter region containing this site by chromatin immunoprecipitation assays. We have demonstrated a novel regulatory mechanism for VEGFA transcription by OASIS in human retinal pigment epithelial cells. Chemical compounds that regulate the binding of OASIS to the promoter region of the VEGFA gene may have potential as therapeutic agents for ocular diseases with neovascularization.

(PDF emailed within 0-6 h: $19.90)

Accession: 056637468

Download citation: RISBibTeXText

PMID: 23383089

DOI: 10.1371/journal.pone.0055155


Related references

The endoplasmic reticulum stress transducer OASIS is involved in the terminal differentiation of goblet cells in the large intestine. Journal of Biological Chemistry 287(11): 8144-8153, 2012

Roles of the endoplasmic reticulum stress transducer OASIS in fracture healing. Bone 49(4): 724-732, 2011

OASIS, an endoplasmic reticulum stress transducer, is involved in normal bone formation. 2007

Physiological functions of endoplasmic reticulum stress transducer OASIS in central nervous system. Anatomical Science International 89(1): 11-20, 2014

Roles of the Endoplasmic Reticulum Stress Transducer OASIS in Ossification of the Posterior Longitudinal Ligament. Clinical Spine Surgery (): -, 2016

Increased susceptibility to dextran sulfate sodium-induced colitis in the endoplasmic reticulum stress transducer OASIS deficient mice. Plos One 9(2): E88048, 2014

Increased expression of tight junctions in ARPE-19 cells under endoplasmic reticulum stress. Current Eye Research 36(12): 1153-1163, 2012

Transcriptional regulation of the endoplasmic reticulum stress gene chop in pancreatic insulin-producing cells. Diabetes 56(4): 1069-1077, 2007

Master regulator for chondrogenesis, Sox9, regulates transcriptional activation of the endoplasmic reticulum stress transducer BBF2H7/CREB3L2 in chondrocytes. Journal of Biological Chemistry 289(20): 13810-13820, 2014

Cytokines downregulate the sarcoendoplasmic reticulum pump Ca2+ ATPase 2b and deplete endoplasmic reticulum Ca2+, leading to induction of endoplasmic reticulum stress in pancreatic beta-cells. Diabetes 54(2): 452-461, 2005

Transcriptional regulation of activating transcription factor 4 under oxidative stress in retinal pigment epithelial ARPE-19/HPV-16 cells. Investigative Ophthalmology and Visual Science 52(3): 1226-1234, 2011

Transcriptional regulation of the Grp78 promoter by endoplasmic reticulum stress: role of TFII-I and its tyrosine phosphorylation. Journal of Biological Chemistry 280(17): 16821-8, 2005

Transcriptional Regulation of the Grp78 Promoter by Endoplasmic Reticulum Stress. Role of TFII-I and Tyrosine Phosphorylation. The Journal of Biological Chemistry 280(17): 821-8, 2005

Pancreatic and duodenal homeobox protein 1 (Pdx-1) maintains endoplasmic reticulum calcium levels through transcriptional regulation of sarco-endoplasmic reticulum calcium ATPase 2b (SERCA2b) in the islet β cell. Journal of Biological Chemistry 289(47): 32798-32810, 2015

Endoplasmic reticulum redox state is not perturbed by pharmacological or pathological endoplasmic reticulum stress in live pancreatic β-cells. Plos One 7(11): E48626, 2013