Ray P E, Bruggeman L A, Weeks B S, Kopp J B, Bryant J L, Owens J W, Notkins A L, Klotman P E
Viral Pathogenesis Unit, National Institute of Dental Research, National Institutes of Health, Bethesda, Maryland.
Kidney Int. 1994 Sep;46(3):759-72. doi: 10.1038/ki.1994.331.
HIV-associated nephropathy is characterized by extensive tubulointerstitial disease with epithelial cell injury, microcystic proliferation, and tubular regeneration with glomerulosclerosis. To explore the role of bFGF as a mediator of HIV-induced interstitial disease, we utilized an HIV transgenic mouse model that manifests clinical and histological features observed in patients. In transgenic mice, simultaneous renal epithelial cell proliferation and injury were detected in vivo. In areas of microcystic proliferation, immunoreactive bFGF colocalized with extracellular matrix. Kidneys from transgenic mice had increased bFGF low affinity binding sites, particularly in the renal interstitium. In vitro, transgenic renal tubular epithelial cells proliferated more rapidly and generated tubular structures spontaneously, in marked contrast to nontransgenic renal cells where these pathologic features could be mimicked by exogenous bFGF. These studies suggest that renal bFGF and its receptors play an important role in the pathogenesis of HIV-associated nephropathy.
HIV相关性肾病的特征是广泛的肾小管间质疾病，伴有上皮细胞损伤、微囊肿增生以及肾小球硬化伴肾小管再生。为了探究碱性成纤维细胞生长因子（bFGF）作为HIV诱导的间质疾病介质的作用，我们利用了一种HIV转基因小鼠模型，该模型表现出患者中观察到的临床和组织学特征。在转基因小鼠中，体内同时检测到肾上皮细胞增殖和损伤。在微囊肿增生区域，免疫反应性bFGF与细胞外基质共定位。转基因小鼠的肾脏具有增加的bFGF低亲和力结合位点，特别是在肾间质中。在体外，转基因肾小管上皮细胞增殖更快并自发形成管状结构，这与非转基因肾细胞形成鲜明对比，在非转基因肾细胞中，这些病理特征可被外源性bFGF模拟。这些研究表明，肾脏bFGF及其受体在HIV相关性肾病的发病机制中起重要作用。
