Gesualdo L, Di Paolo S, Calabró A, Milani S, Maiorano E, Ranieri E, Pannarale G, Schena F P
Institute of Nephrology, University of Bari, Italy.
Kidney Int. 1996 Mar;49(3):656-65. doi: 10.1038/ki.1996.94.
The kidney is one of the major sites of EGF production and there it seems to play several biological functions, such as modulation of cell growth, renal repair following injury, regulation of cellular metabolism and glomerular haemodinamics. The present study was first aimed at localizing EGF and its receptor (R) in normal human kidney by immunohistochemical and in situ hybridization techniques. Then, the distribution of the growth factor and its R was explored in biopsy specimens from eight patients with acute tubulointerstitial damage. In the normal human kidney, both EGF immunoreactivity and EGF mRNA were localized in tubular profiles corresponding to Henle's loop and, although to a lesser intensity, to distal convoluted tubule. EGF immunostaining was remarkable mainly at the apical surface of tubular cells. EGF-R protein expression was detected in glomerular endothelial cells, in peritubular capillaries and arteriolar walls, as well as along the thick ascending limb of Henle's lop and distal convoluted tubule, where it colocalized with Tamm-Horsfall protein. Immunohistochemical analysis of tubular profiles revealed that EGF-R was located especially along the basolateral membrane of tubular cells and within the basal part of cytoplasm. Endogenous alkaline phosphatase and CHIP28 positive tubules did not show any signal for EGF and its receptor. Kidneys with acute tubulointerstitial injury exhibited a dramatic decrease of EGF expression, whereas EGF-R showed only minor modifications. Interestingly, EGF-R was localized to both apical and antiluminal membranes of positive tubular cells. It is concluded that EGF-EGF receptor loop may be relevant in the pathogenesis of acute tubulointerstitial damage and recovery from tubular injury, while its role in the physiological renewal of the urothelium remains speculative.
肾脏是表皮生长因子（EGF）产生的主要部位之一，在那里它似乎发挥着多种生物学功能，如调节细胞生长、损伤后肾脏修复、调节细胞代谢和肾小球血液动力学。本研究首先旨在通过免疫组织化学和原位杂交技术在正常人类肾脏中定位EGF及其受体（R）。然后，在8例急性肾小管间质性损伤患者的活检标本中探索生长因子及其受体的分布。在正常人类肾脏中，EGF免疫反应性和EGF mRNA均定位于与髓袢相对应的肾小管结构中，虽然强度较小，但也定位于远曲小管。EGF免疫染色主要在肾小管细胞的顶端表面显著。在肾小球内皮细胞、肾小管周围毛细血管和小动脉壁以及髓袢升支粗段和远曲小管中检测到EGF-R蛋白表达，在这些部位它与Tamm-Horsfall蛋白共定位。对肾小管结构的免疫组织化学分析显示，EGF-R特别位于肾小管细胞的基底外侧膜和细胞质基部内。内源性碱性磷酸酶和CHIP28阳性肾小管未显示出EGF及其受体的任何信号。急性肾小管间质性损伤的肾脏表现出EGF表达显著降低，而EGF-R仅显示出轻微改变。有趣的是，EGF-R定位于阳性肾小管细胞的顶端膜和反腔膜。结论是EGF-EGF受体环路可能与急性肾小管间质性损伤的发病机制和肾小管损伤的恢复有关，而其在尿路上皮生理更新中的作用仍属推测。
