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BIGH3 protein and macrophages in retinal endothelial cell apoptosis

Overview of attention for article published in Apoptosis, November 2014
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Title
BIGH3 protein and macrophages in retinal endothelial cell apoptosis
Published in
Apoptosis, November 2014
DOI 10.1007/s10495-014-1052-6
Pubmed ID
Authors

Albert A. Mondragon, Brandi S. Betts-Obregon, Robert J. Moritz, Kalpana Parvathaneni, Mary M. Navarro, Hong Seok Kim, Chi Fung Lee, Richard G. LeBaron, Reto Asmis, Andrew T. Tsin

Abstract

Diabetes is a pandemic disease with a higher occurrence in minority populations. The molecular mechanism to initiate diabetes-associated retinal angiogenesis remains largely unknown. We propose an inflammatory pathway of diabetic retinopathy in which macrophages in the diabetic eye provide TGFβ to retinal endothelial cells (REC) in the retinal microvasculature. In response to TGFβ, REC synthesize and secrete a pro-apoptotic BIGH3 (TGFβ-Induced Gene Human Clone 3) protein, which acts in an autocrine loop to induce REC apoptosis. Rhesus monkey retinal endothelial cells (RhREC) were treated with dMCM (cell media of macrophages treated with high glucose and LDL) and assayed for apoptosis (TUNEL), BIGH3 mRNA (qPCR), and protein (Western blots) expressions. Cells were also treated with ΤGFβ1 and 2 for BIGH3 mRNA and protein expression. Inhibition assays were carried out using antibodies for TGFβ1 and for BIGH3 to block apoptosis and mRNA expression. BIGH3 in cultured RhREC cells were identified by immunohistochemistry (IHC). Distribution of BIGH3 and macrophages in the diabetic mouse retina was examined with IHC. RhRECs treated with dMCM or TGFβ showed a significant increase in apoptosis and BIGH3 protein expression. Recombinant BIGH3 added to RhREC culture medium led to a dose-dependent increase in apoptosis. Antibodies (Ab) directed against BIGH3 and TGFβ, as well as TGFβ receptor blocker resulted in a significant reduction in apoptosis induced by either dMCM, TGFβ or BIGH3. IHC showed that cultured RhREC constitutively expressed BIGH3. Macrophage and BIGH3 protein were co-localized to the inner retina of the diabetic mouse eye. Our results support a novel inflammatory pathway for diabetic retinopathy. This pathway is initiated by TGFβ released from macrophages, which promotes synthesis and release of BIGH3 protein by REC and REC apoptosis.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 22 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 22 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 4 18%
Student > Ph. D. Student 3 14%
Student > Master 3 14%
Professor 2 9%
Student > Bachelor 1 5%
Other 4 18%
Unknown 5 23%
Readers by discipline Count As %
Medicine and Dentistry 5 23%
Biochemistry, Genetics and Molecular Biology 4 18%
Agricultural and Biological Sciences 2 9%
Neuroscience 2 9%
Pharmacology, Toxicology and Pharmaceutical Science 1 5%
Other 1 5%
Unknown 7 32%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 November 2014.
All research outputs
#20,243,777
of 22,771,140 outputs
Outputs from Apoptosis
#631
of 803 outputs
Outputs of similar age
#219,364
of 262,839 outputs
Outputs of similar age from Apoptosis
#8
of 15 outputs
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So far Altmetric has tracked 803 research outputs from this source. They receive a mean Attention Score of 3.6. This one is in the 1st percentile – i.e., 1% of its peers scored the same or lower than it.
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We're also able to compare this research output to 15 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.