Bcl-2 Expression in Pericytes and Astrocytes Impacts Vascular Development and Homeostasis
Autor: | Andrew Suscha, Nasim Jamali, Volkhard Lindner, Nader Sheibani, Ismail Zaitoun, Christine M. Sorenson, Catherine M. Wintheiser, Soesiawati R. Darjatmoko, Katherine Schleck, Shoujian Wang, Barbara A. Hanna |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Male Angiogenesis Science Apoptosis Biology Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Retinal Diseases Ischemia medicine Animals Allele Cell Proliferation Mice Knockout Cell lineage Retina Multidisciplinary Neovascularization Pathologic Retinal Vessels Retinal medicine.disease Choroidal Neovascularization Lymphoma Oxygen 030104 developmental biology Choroidal neovascularization medicine.anatomical_structure chemistry Proto-Oncogene Proteins c-bcl-2 Astrocytes Cancer research Medicine Female Endothelium Vascular medicine.symptom Pericytes 030217 neurology & neurosurgery Homeostasis |
Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
ISSN: | 2045-2322 |
Popis: | B-cell lymphoma 2 (Bcl-2) protein is the founding member of a group of proteins known to modulate apoptosis. Its discovery set the stage for identification of family members with either pro- or anti-apoptotic properties. Expression of Bcl-2 plays an important role during angiogenesis by influencing not only vascular cell survival, but also migration and adhesion. Although apoptosis and migration are postulated to have roles during vascular remodeling and regression, the contribution of Bcl-2 continues to emerge. We previously noted that the impaired retinal vascularization and an inability to undergo pathologic neovascularization observed in mice globally lacking Bcl-2 did not occur when mice lacked the expression of Bcl-2 only in endothelial cells. To further examine the effect of Bcl-2 expression during vascularization of the retina, we assessed its contribution in pericytes or astrocytes by generating mice with a conditional Bcl-2 allele (Bcl-2Flox/Flox) and Pdgfrb-cre (Bcl-2PC mice) or Gfap-cre (Bcl-2AC mice). Bcl-2PC and Bcl-2AC mice demonstrated increased retinal vascular cell apoptosis, reduced numbers of pericytes and endothelial cells and fewer arteries and veins in the retina. Bcl-2PC mice also demonstrated delayed advancement of the superficial retinal vascular layer and aberrant vascularization of the deep vascular plexus and central retina. Although pathologic neovascularization in oxygen-induced ischemic retinopathy (OIR) was not affected by lack of expression of Bcl-2 in either pericytes or astrocytes, laser-induced choroidal neovascularization (CNV) was significantly reduced in Bcl-2PC mice compared to littermate controls. Together these studies begin to reveal how cell autonomous modulation of apoptosis in vascular cells impacts development and homeostasis. |
Databáze: | OpenAIRE |
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