Barnes J L, Hastings R R, De la Garza M A
Department of Medicine, University of Texas Health Science Center, San Antonio 78284.
Am J Pathol. 1994 Sep;145(3):585-97.
Fibronectin (Fn) regulates cell migration, proliferation, and extracellular matrix formation during embryogenesis, angiogenesis, and wound healing. Fn also promotes mesangial cell migration and proliferation in vitro and contributes to extracellular matrix formation and tissue remodeling during glomerular disease. In this study, we examined, by immunohistochemistry and in situ hybridization, the temporal glomerular localization and cellular sources of Fn in Habu snake venom (HSV)-induced proliferative glomerulonephritis. Early HSV-induced glomerular lesions consisted of microaneurysms devoid of resident glomerular cells and filled with platelets, leukocytes, and erythrocytes. Over the course of the disease, mesangial cells migrated into the lesions, proliferated, and formed a confluent cellular mass. Fn was present in lesions beginning at 8 hours, with highest intensity at 72 hours and diminishing at 2 weeks after HSV. Staining for Fn at 8 and 24 hours after HSV was attributed to platelets and macrophages. In situ hybridization and phenotypic identification of cell types within lesions revealed macrophages as the predominant source of cellular Fn mRNA at these times. At 48 hours after HSV, Fn mRNA was expressed in proliferating mesangial cells in addition to macrophages. Most cells in lesions at 72 hours after HSV were mesangial, at a time when expression of Fn mRNA peaked. Cellular expression for Fn mRNA and translated protein declined at 2 weeks after HSV. These studies support the hypothesis that Fn, derived from platelets and macrophages, provides a provisional matrix involved with mesangial cell migration into glomerular lesions. Fn produced by mesangial cells might contribute to the formation of a stable extracellular matrix.
纤连蛋白（Fn）在胚胎发育、血管生成和伤口愈合过程中调节细胞迁移、增殖以及细胞外基质的形成。Fn还能促进体外系膜细胞的迁移和增殖，并在肾小球疾病中参与细胞外基质的形成和组织重塑。在本研究中，我们通过免疫组织化学和原位杂交技术，检测了在蝮蛇毒（HSV）诱导的增殖性肾小球肾炎中Fn在肾小球的定位时间及细胞来源。早期HSV诱导的肾小球病变表现为微动脉瘤，其中没有驻留的肾小球细胞，而是充满了血小板、白细胞和红细胞。在疾病发展过程中，系膜细胞迁移到病变部位，增殖并形成融合的细胞团。Fn在HSV感染后8小时开始出现在病变中，72小时时强度最高，2周后减弱。HSV感染后8小时和24小时Fn的染色归因于血小板和巨噬细胞。原位杂交和病变内细胞类型的表型鉴定显示，此时巨噬细胞是细胞Fn mRNA的主要来源。HSV感染后48小时，除巨噬细胞外，增殖的系膜细胞中也表达Fn mRNA。HSV感染后72小时病变中的大多数细胞是系膜细胞，此时Fn mRNA的表达达到峰值。HSV感染后2周，Fn mRNA的细胞表达和翻译蛋白均下降。这些研究支持了这样的假说，即源自血小板和巨噬细胞的Fn提供了一种与系膜细胞迁移到肾小球病变相关的临时基质。系膜细胞产生的Fn可能有助于形成稳定的细胞外基质。
