دورية أكاديمية
أعرض في EDS

RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity.

التفاصيل البيبلوغرافية
العنوان: RNA-Seq Provides Insights into VEGF-Induced Signaling in Human Retinal Microvascular Endothelial Cells: Implications in Retinopathy of Prematurity.
المؤلفون: Ramshekar A; Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132, USA., Bretz CA; Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132, USA., Hartnett ME; Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah, 65 Mario Capecchi Dr, Salt Lake City, UT 84132, USA.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2022 Jul 01; Vol. 23 (13). Date of Electronic Publication: 2022 Jul 01.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Retinal Neovascularization*/metabolism , Retinopathy of Prematurity*/genetics , Retinopathy of Prematurity*/metabolism, Animals ; Disease Models, Animal ; Endothelial Cells/metabolism ; Humans ; Infant, Newborn ; Neovascularization, Pathologic/metabolism ; RNA-Seq ; Rats ; Rats, Sprague-Dawley ; Retinal Vessels/metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism
مستخلص: The pathophysiology of retinopathy of prematurity (ROP) is postulated to first involve delayed intraretinal vascularization, followed by intravitreal neovascularization (IVNV). Although intravitreal agents that reduce the bioactivity of vascular endothelial growth factor (VEGF) are used to treat IVNV, concerns exist regarding their effects on intraretinal vascularization. In an experimental ROP model, VEGF receptor 2 (VEGFR2) knockdown in retinal endothelial cells reduced IVNV and promoted intraretinal vascularization, whereas knockdown of a downstream effector, signal transducer and activator of transcription 3 (STAT3) in retinal endothelial cells only reduced IVNV. In this study, we tested the hypothesis that the different pathways involved in VEGF-triggered VEGFR2 signaling and VEGF-triggered STAT3 signaling in retinal endothelial cells would allow us to delineate signaling pathways involved in IVNV from those involved in intraretinal vascularization in ROP. To address our hypothesis, we used RNA-sequencing and pathway enrichment analysis to determine changes in the transcriptome of cultured human retinal microvascular endothelial cells (HRMECs). Of the enriched pathways, inactivation of oncostatin M signaling was predicted by either KDR or STAT3 knockdown in the presence of VEGF. Activation of kinetochore metaphase signaling was predicted by KDR knockdown, whereas inactivation was predicted by STAT3 knockdown in the presence of VEGF. Inactivation of signaling by the Rho family of GTPases was predicted by KDR knockdown, but activation was predicted by STAT3 knockdown in the presence of VEGF. Taken together, our data identified unique signaling pathway differences between VEGF-triggered VEGFR2 and VEGF-triggered STAT3 in HRMECs that might have implications in ROP.
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معلومات مُعتمدة: R01 EY015130 United States EY NEI NIH HHS; T32 EY024234 United States EY NEI NIH HHS; R01EY017011 United States EY NEI NIH HHS; P30 EY014800 United States EY NEI NIH HHS; R01 EY017011 United States EY NEI NIH HHS; P30EY014800 United States EY NEI NIH HHS; F30EY032311 United States EY NEI NIH HHS; R01EY015130 United States EY NEI NIH HHS; N/A Research to Prevent Blindness; F30 EY032311 United States EY NEI NIH HHS
فهرسة مساهمة: Keywords: HRMECs; KDR; RNA-seq; ROP; STAT3; VEGF; VEGFR2
المشرفين على المادة: 0 (Vascular Endothelial Growth Factor A)
تواريخ الأحداث: Date Created: 20220709 Date Completed: 20220712 Latest Revision: 20230221
رمز التحديث: 20230221
مُعرف محوري في PubMed: PMC9266443
DOI: 10.3390/ijms23137354
PMID: 35806359
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms23137354