Seifert R A, Alpers C E, Bowen-Pope D F
Department of Pathology, University of Washington, Seattle 98195, USA.
Kidney Int. 1998 Sep;54(3):731-46. doi: 10.1046/j.1523-1755.1998.00046.x.
Experimental analysis of gene function is increasingly being accomplished using mouse models. Glomerular malformations occur in mice in which the platelet-derived growth factor (PDGF) B-chain gene or the PDGF receptor beta-subunit gene have been deleted. To understand potential PDGF signaling pathways in the kidney, we determined the expression pattern of PDGF ligand and receptor genes in mouse kidney during development and in the mature adult kidney.
We used in situ hybridization to map the expression of transcripts encoding the PDGF ligands (A-chain and B-chain) and PDGF receptors (PDGFRalpha and PDGFRbeta) in the developing and mature kidney of the mouse.
PDGF A-chain transcripts are expressed by epithelial cells (especially in what appear to be the loop of Henle) and possibly in vascular smooth muscle cells. Its receptor, PDGFRalpha, is expressed by interstitial cells. PDGF B-chain transcripts are most highly expressed by vascular endothelial cells of developing and adult kidney and minimally by visceral epithelia of immature glomeruli. PDGFRbeta transcripts are expressed by fetal blastemal cells, interstitial cells, mesangial cells, and vascular smooth muscle cells and by adult mesangial and interstitial cells. PDGFRalpha and PDGFRbeta expression is especially prominent in lipid-laden interstitial cells in the adult kidney.
These patterns of expression are similar, but not identical, to those observed in rat and human and suggest that paracrine interactions mediated by the PDGF/PDGF receptor system may coordinate the development of the tubular, vascular, and interstitial components during kidney development and disease.
利用小鼠模型对基因功能进行实验分析的情况日益增多。在血小板衍生生长因子(PDGF)B链基因或PDGF受体β亚基基因缺失的小鼠中会出现肾小球畸形。为了解肾脏中潜在的PDGF信号通路,我们确定了PDGF配体和受体基因在小鼠肾脏发育过程及成年成熟肾脏中的表达模式。
我们采用原位杂交技术来定位编码PDGF配体(A链和B链)和PDGF受体(PDGFRα和PDGFRβ)的转录本在小鼠发育中和成熟肾脏中的表达情况。
PDGF A链转录本由上皮细胞表达(尤其在看似亨氏袢的结构中),也可能由血管平滑肌细胞表达。其受体PDGFRα由间质细胞表达。PDGF B链转录本在发育中和成年肾脏的血管内皮细胞中表达最高,在未成熟肾小球的脏层上皮细胞中表达最低。PDGFRβ转录本由胎儿胚基细胞、间质细胞、系膜细胞和血管平滑肌细胞表达,在成年系膜细胞和间质细胞中也有表达。PDGFRα和PDGFRβ在成年肾脏富含脂质的间质细胞中的表达尤为突出。
这些表达模式与在大鼠和人类中观察到的模式相似但不完全相同,提示由PDGF/PDGF受体系统介导的旁分泌相互作用可能在肾脏发育和疾病过程中协调肾小管、血管和间质成分的发育。