Lindblom Per, Gerhardt Holger, Liebner Stefan, Abramsson Alexandra, Enge Maria, Hellstrom Mats, Backstrom Gudrun, Fredriksson Simon, Landegren Ulf, Nystrom Henrik C, Bergstrom Goran, Dejana Elisabetta, Ostman Arne, Lindahl Per, Betsholtz Christer
Department of Medical Biochemistry, Göteborg University, Göteborg SE-405 30, Sweden.
Genes Dev. 2003 Aug 1;17(15):1835-40. doi: 10.1101/gad.266803.
Several platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) family members display C-terminal protein motifs that confer retention of the secreted factors within the pericellular space. To address the role of PDGF-B retention in vivo, we deleted the retention motif by gene targeting in mice. This resulted in defective investment of pericytes in the microvessel wall and delayed formation of the renal glomerulus mesangium. Long-term effects of lack of PDGF-B retention included severe retinal deterioration, glomerulosclerosis, and proteinuria. We conclude that retention of PDGF-B in microvessels is essential for proper recruitment and organization of pericytes and for renal and retinal function in adult mice.
几种血小板衍生生长因子(PDGF)和血管内皮生长因子(VEGF)家族成员具有C端蛋白基序,可使分泌因子保留在细胞周围空间内。为了研究PDGF-B保留在体内的作用,我们通过基因靶向删除了小鼠中的保留基序。这导致周细胞在微血管壁中的包绕缺陷,并延迟了肾小球系膜的形成。缺乏PDGF-B保留的长期影响包括严重的视网膜退化、肾小球硬化和蛋白尿。我们得出结论,PDGF-B在微血管中的保留对于成年小鼠周细胞的正常募集和组织以及肾脏和视网膜功能至关重要。