Lee Seung-Hun, Jung Ju-Young, Han Ki-Hwan, Yang Chul-Woo, Choi Kyu-Bok, Kim Jin
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Am J Nephrol. 2004 Mar-Apr;24(2):212-20. doi: 10.1159/000077275. Epub 2004 Mar 11.
Apoptosis plays an important role in the morphogenesis of the renal papilla. During kidney development, ATL is derived from the TAL in the inner medulla by apoptotic deletion of a fraction of TAL cells and the transformation of the remaining TAL cells. EGF is an important regulator of apoptosis in the kidney.
Exogenously administered EGF in postnatal rat affects renal papilla growth with cell proliferation and apoptosis in the loop of Henle.
Rat pups received subcutaneous injections of EGF (0.3 microg/g body weight) or saline four times a day from after birth. Rats were sacrificed and the kidneys were preserved for immunohistochemistry on day 4 and day 7. The TAL was identified with antibody directed against Na-K-ATPase or BSC1, and type A intercalated cells were identified with antibody to anion exchanger 1 (AE1). Apoptosis was detected with TUNEL method, and cell proliferation with immunostaining for PCNA. RESULTS--PRIMARY AND SECONDARY: EGF treatment resulted in the following: (1) reduced kidney weight; (2) shortened length of renal papilla; (3) delayed transformation of the cuboidal epithelium into the squamous epithelium of the ATL; (4) delayed elimination of type A intercalated cells in the medullary collecting duct; (5) decreased both apoptotic index and PCNA-positive cells in the TAL and the collecting duct of the renal medulla.
These findings suggest that exogenous EGF delays the development of loop of Henle in the renal papilla by reducing both apoptosis and cell proliferation.
细胞凋亡在肾乳头的形态发生中起重要作用。在肾脏发育过程中,升支粗段(ATL)由髓质内层的髓袢升支粗段(TAL)通过部分TAL细胞的凋亡性缺失以及其余TAL细胞的转化而形成。表皮生长因子(EGF)是肾脏细胞凋亡的重要调节因子。
出生后大鼠外源性给予EGF会影响肾乳头生长,并伴有髓袢细胞增殖和凋亡。
出生后的大鼠幼崽每天接受4次皮下注射EGF(0.3微克/克体重)或生理盐水。在第4天和第7天处死大鼠并保存肾脏用于免疫组织化学分析。用抗Na-K-ATP酶或BSC1抗体鉴定TAL,用抗阴离子交换蛋白1(AE1)抗体鉴定A型闰细胞。用TUNEL法检测细胞凋亡,用PCNA免疫染色检测细胞增殖。结果——主要和次要:EGF治疗导致以下结果:(1)肾脏重量减轻;(2)肾乳头长度缩短;(3)立方上皮向ATL鳞状上皮的转化延迟;(4)髓质集合管中A型闰细胞的清除延迟;(5)肾髓质TAL和集合管中的凋亡指数和PCNA阳性细胞均减少。
这些发现表明,外源性EGF通过减少细胞凋亡和细胞增殖而延迟肾乳头髓袢的发育。