Goodyer P R, Kachra Z, Bell C, Rozen R
Department of Pediatrics, McGill University-Montreal Children's Hospital Research Institute, Quebec, Canada.
Am J Physiol. 1988 Dec;255(6 Pt 2):F1191-6. doi: 10.1152/ajprenal.1988.255.6.F1191.
Epidermal growth factor (EGF) is a potent polypeptide mitogen with various receptor-mediated growth effects on cells from the skin, breast, and gastrointestinal tract. Recent studies indicate that EGF is produced in the kidney and is excreted in the urine, but the biological significance of renal EGF is uncertain. We demonstrate in vitro mitogenicity of EGF for LLC-PK1 cells, a tubular epithelial cell line derived from pig kidney cortex. Furthermore, when subconfluent monolayers of LLC-PK1 cells are exposed to EGF for 24 h, sodium-dependent phosphate transport is stimulated (209-410% of control). These cells possess EGF-specific high-affinity binding sites at their surface (Kd 300-700 pM) but cannot synthesize the growth factor. EGF binding sites are not a peculiarity of the LLC-PK1 cell line, since similar sites are present on MDCK cells (derived from dog kidney distal tubule or collecting duct), primary cultures of mouse proximal tubular cells, and freshly prepared membrane fractions from mouse kidney. Cortical basolateral membranes are highly enriched in EGF binding sites, whereas EGF binding by brush-border membrane fractions is minimal and is compatible with contamination.
表皮生长因子(EGF)是一种强效的多肽促细胞分裂剂,对来自皮肤、乳腺和胃肠道的细胞具有多种受体介导的生长效应。最近的研究表明,EGF在肾脏中产生并经尿液排泄,但肾脏EGF的生物学意义尚不确定。我们证明了EGF对LLC-PK1细胞具有体外促有丝分裂活性,LLC-PK1细胞是一种源自猪肾皮质的肾小管上皮细胞系。此外,当LLC-PK1细胞的亚汇合单层暴露于EGF 24小时时,钠依赖性磷酸盐转运受到刺激(为对照的209 - 410%)。这些细胞在其表面具有EGF特异性高亲和力结合位点(解离常数Kd为300 - 700 pM),但不能合成生长因子。EGF结合位点并非LLC-PK1细胞系所特有,因为在MDCK细胞(源自犬肾远曲小管或集合管)、小鼠近端肾小管细胞原代培养物以及从小鼠肾脏新鲜制备的膜组分中也存在类似位点。皮质基底外侧膜中EGF结合位点高度富集,而刷状缘膜组分的EGF结合极少,且与污染情况相符。