Matches in SemOpenAlex for { <https://semopenalex.org/work/W4367314882> ?p ?o ?g. }
- W4367314882 endingPage "1279" @default.
- W4367314882 startingPage "1279" @default.
- W4367314882 abstract "Bone Morphogenetic Protein 4 (BMP4) is a secreted growth factor of the Transforming Growth Factor beta (TGFβ) superfamily. The goal of this study was to test whether BMP4 contributes to the pathogenesis of diabetic retinopathy (DR). Immunofluorescence of BMP4 and the vascular marker isolectin-B4 was conducted on retinal sections of diabetic and non-diabetic human and experimental mice. We used Akita mice as a model for type-1 diabetes. Proteins were extracted from the retina of postmortem human eyes and 6-month diabetic Akita mice and age-matched control. BMP4 levels were measured by Western blot (WB). Human retinal endothelial cells (HRECs) were used as an in vitro model. HRECs were treated with BMP4 (50 ng/mL) for 48 h. The levels of phospho-smad 1/5/9 and phospho-p38 were measured by WB. BMP4-treated and control HRECs were also immunostained with anti-Zo-1. We also used electric cell-substrate impedance sensing (ECIS) to calculate the transcellular electrical resistance (TER) under BMP4 treatment in the presence and absence of noggin (200 ng/mL), LDN193189 (200 nM), LDN212854 (200 nM) or inhibitors of vascular endothelial growth factor receptor 2 (VEGFR2; SU5416, 10 μM), p38 (SB202190, 10 μM), ERK (U0126, 10 μM) and ER stress (Phenylbutyric acid or PBA, 30 μmol/L). The impact of BMP4 on matrix metalloproteinases (MMP2 and MMP9) was also evaluated using specific ELISA kits. Immunofluorescence of human and mouse eyes showed increased BMP4 immunoreactivity, mainly localized in the retinal vessels of diabetic humans and mice compared to the control. Western blots of retinal proteins showed a significant increase in BMP4 expression in diabetic humans and mice compared to the control groups (p < 0.05). HRECs treated with BMP4 showed a marked increase in phospho-smad 1/5/9 (p = 0.039) and phospho-p38 (p = 0.013). Immunofluorescence of Zo-1 showed that BMP4-treated cells exhibited significant barrier disruption. ECIS also showed a marked decrease in TER of HRECs by BMP4 treatment compared to vehicle-treated HRECs (p < 0.001). Noggin, LDN193189, LDN212854, and inhibitors of p38 and VEGFR2 significantly mitigated the effects of BMP4 on the TER of HRECs. Our finding provides important insights regarding the role of BMP4 as a potential player in retinal endothelial cell dysfunction in diabetic retinopathy and could be a novel target to preserve the blood-retinal barrier during diabetes." @default.
- W4367314882 created "2023-04-29" @default.
- W4367314882 creator A5001248425 @default.
- W4367314882 creator A5012822338 @default.
- W4367314882 creator A5016740392 @default.
- W4367314882 creator A5038843185 @default.
- W4367314882 creator A5046990139 @default.
- W4367314882 creator A5055493656 @default.
- W4367314882 creator A5080123289 @default.
- W4367314882 creator A5087012334 @default.
- W4367314882 date "2023-04-28" @default.
- W4367314882 modified "2023-09-30" @default.
- W4367314882 title "Bone Morphogenetic Protein-4 Impairs Retinal Endothelial Cell Barrier, a Potential Role in Diabetic Retinopathy" @default.
- W4367314882 cites W1534365984 @default.
- W4367314882 cites W1825203150 @default.
- W4367314882 cites W1973203818 @default.
- W4367314882 cites W1977898942 @default.
- W4367314882 cites W1989144642 @default.
- W4367314882 cites W1989394732 @default.
- W4367314882 cites W2001398097 @default.
- W4367314882 cites W2015160990 @default.
- W4367314882 cites W2019777614 @default.
- W4367314882 cites W2020653182 @default.
- W4367314882 cites W2020777546 @default.
- W4367314882 cites W2023589430 @default.
- W4367314882 cites W2037595837 @default.
- W4367314882 cites W2056754736 @default.
- W4367314882 cites W2057336811 @default.
- W4367314882 cites W2059460453 @default.
- W4367314882 cites W2082152178 @default.
- W4367314882 cites W2082764627 @default.
- W4367314882 cites W2083668209 @default.
- W4367314882 cites W2087187911 @default.
- W4367314882 cites W2122810132 @default.
- W4367314882 cites W2217062597 @default.
- W4367314882 cites W2286749487 @default.
- W4367314882 cites W2338795774 @default.
- W4367314882 cites W2460275535 @default.
- W4367314882 cites W2564655258 @default.
- W4367314882 cites W2589146052 @default.
- W4367314882 cites W2590927443 @default.
- W4367314882 cites W2593871081 @default.
- W4367314882 cites W2594136532 @default.
- W4367314882 cites W2599008286 @default.
- W4367314882 cites W2599889833 @default.
- W4367314882 cites W2605885132 @default.
- W4367314882 cites W2738269839 @default.
- W4367314882 cites W2794409568 @default.
- W4367314882 cites W2893145088 @default.
- W4367314882 cites W2974661394 @default.
- W4367314882 cites W2982449243 @default.
- W4367314882 cites W2995077780 @default.
- W4367314882 cites W3016952166 @default.
- W4367314882 cites W3023029088 @default.
- W4367314882 cites W3033065537 @default.
- W4367314882 cites W3042749239 @default.
- W4367314882 cites W3045569242 @default.
- W4367314882 cites W3101341162 @default.
- W4367314882 cites W3117437033 @default.
- W4367314882 cites W3127096249 @default.
- W4367314882 cites W3128701769 @default.
- W4367314882 cites W3189707785 @default.
- W4367314882 cites W3190384914 @default.
- W4367314882 cites W4205682033 @default.
- W4367314882 cites W4211160592 @default.
- W4367314882 cites W4223650987 @default.
- W4367314882 cites W4224260624 @default.
- W4367314882 cites W4283215871 @default.
- W4367314882 cites W4292080973 @default.
- W4367314882 doi "https://doi.org/10.3390/cells12091279" @default.
- W4367314882 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/37174679" @default.
- W4367314882 hasPublicationYear "2023" @default.
- W4367314882 type Work @default.
- W4367314882 citedByCount "0" @default.
- W4367314882 crossrefType "journal-article" @default.
- W4367314882 hasAuthorship W4367314882A5001248425 @default.
- W4367314882 hasAuthorship W4367314882A5012822338 @default.
- W4367314882 hasAuthorship W4367314882A5016740392 @default.
- W4367314882 hasAuthorship W4367314882A5038843185 @default.
- W4367314882 hasAuthorship W4367314882A5046990139 @default.
- W4367314882 hasAuthorship W4367314882A5055493656 @default.
- W4367314882 hasAuthorship W4367314882A5080123289 @default.
- W4367314882 hasAuthorship W4367314882A5087012334 @default.
- W4367314882 hasBestOaLocation W43673148821 @default.
- W4367314882 hasConcept C104317684 @default.
- W4367314882 hasConcept C118131993 @default.
- W4367314882 hasConcept C118487528 @default.
- W4367314882 hasConcept C126322002 @default.
- W4367314882 hasConcept C134018914 @default.
- W4367314882 hasConcept C146285616 @default.
- W4367314882 hasConcept C167734588 @default.
- W4367314882 hasConcept C169760540 @default.
- W4367314882 hasConcept C2777025900 @default.
- W4367314882 hasConcept C2777093970 @default.
- W4367314882 hasConcept C2778761762 @default.
- W4367314882 hasConcept C2779829184 @default.
- W4367314882 hasConcept C2780827179 @default.
- W4367314882 hasConcept C2781080636 @default.