Miller S B, Rogers S A, Estes C E, Hammerman M R
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Am J Physiol. 1992 Jun;262(6 Pt 2):F1032-8. doi: 10.1152/ajprenal.1992.262.6.F1032.
Epidermal growth factor (EGF) precursor is synthesized within kidney in the thick ascending limbs of Henle's loop and in distal tubule. Under baseline conditions EGF precursor is localized to the luminal membrane. In contrast, functional EGF receptors are present in basolateral membranes of sensitive renal cells. Immunostainable EGF is increased in contralateral kidneys following uninephrectomy of rats. To confirm this increase and determine whether the distribution of EGF changes in this setting, we measured immunostainable EGF in kidneys originating from rats 1, 2, 5, or 14 days following unilateral nephrectomy or sham surgery. There was a suggestion of an increase in immunostainable EGF in distal tubules 5 days postnephrectomy and a definite increase 14 days postnephrectomy. At 1 or 2 days postnephrectomy, and following sham surgery, immunostainable EGF was present predominantly at luminal membranes. In contrast, immunostainable EGF was present more diffusely throughout distal tubular cells at 5 and 14 days postnephrectomy and clearly localized adjacent to both luminal and antiluminal membranes in kidneys obtained 14 days postnephrectomy. EGF extractable from kidneys was increased significantly 5 and 14 days postnephrectomy. This material is the size of mature EGF. The altered localization of immunostainable peptide indicates that a redistribution of intracellular EGF accompanies increased synthesis postnephrectomy. Antiluminal EGF precursor or mature EGF present within kidney could act as a paracrine growth factor.
表皮生长因子(EGF)前体在肾脏的髓袢升支粗段和远曲小管中合成。在基线条件下,EGF前体定位于管腔膜。相反,功能性EGF受体存在于敏感肾细胞的基底外侧膜中。大鼠单侧肾切除术后,对侧肾脏中可免疫染色的EGF增加。为了证实这种增加并确定在这种情况下EGF的分布是否发生变化,我们测量了单侧肾切除或假手术后1、2、5或14天大鼠肾脏中可免疫染色的EGF。肾切除术后5天,远曲小管中可免疫染色的EGF有增加的趋势,肾切除术后14天有明显增加。在肾切除术后1或2天以及假手术后,可免疫染色的EGF主要存在于管腔膜。相反,肾切除术后5天和14天,可免疫染色的EGF在整个远曲小管细胞中分布更广泛,在肾切除术后14天获得的肾脏中,明显定位于管腔膜和反管腔膜附近。肾切除术后5天和14天,从肾脏中提取的EGF显著增加。这种物质的大小与成熟EGF相同。可免疫染色肽的定位改变表明,肾切除术后细胞内EGF的重新分布伴随着合成增加。肾脏内存在的反管腔EGF前体或成熟EGF可作为旁分泌生长因子。