Zhang M Z, Wang J L, Cheng H F, Harris R C, McKanna J A
George M. O'Brien Kidney and Urologic Diseases Center, Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Am J Physiol. 1997 Dec;273(6):F994-1002. doi: 10.1152/ajprenal.1997.273.6.F994.
The inducible second isoform of cyclooxygenase (COX-2) that mediates inflammation also is expressed at low levels in normal adult rat kidneys and is upregulated in response to noninflammatory stimuli (R. C. Harris, J. A. McKanna, Y. Akai, H. R. Jacobson, R. N. DuBois, and M. D. Breyer, J. Clin. Invest. 94: 2504-2510, 1994). Roles in morphogenesis are indicated by reported teratogenicity of COX inhibitors and renal dysgenesis in COX-2 knockout mice (J. E. Dinchuk, B. D. Car, R. J. Focht, J. J. Johnston, B. D. Jaffee, M. B. Covington, N. R. Contel, V. M. Eng, R. J. Collins, P. M. Czerniak, A. G. Stewart, and J. M. Trzaskos, Nature 378: 406-409, 1995; S. G. Morham, R. Lagenbach, C. D. Loftin, H. F. Tiano, N. Vouloumanos, J. C. Jennette, J. F. Mahler, K. D. Kluckman, A. Ledford, C. A. Lee, and O. Smithies. Cell 83: 473-482, 1995). Blots from developing rat kidneys demonstrated that COX-2 mRNA and immunoreactive protein were present in neonates, peaked in the 2nd and 3rd postnatal weeks and declined to adult levels by the 3rd month. Immunolocalization and in situ hybridization detected intense COX-2 immunoreactivity and mRNA in a subset of thick ascending limb epithelial cells near the macula densa in each developing nephron; after 2 wk the COX-2 gradually waned. These data demonstrate that COX-2 expression is subject to normal developmental regulation and can be sustained over extended periods; they also support the conclusion that metabolites of COX-2 play important roles in the differentiation and early functions of mammalian nephrons.
介导炎症反应的环氧化酶（COX-2）的诱导性第二种同工型在正常成年大鼠肾脏中也有低水平表达，并在对非炎症刺激的反应中上调（R.C.哈里斯、J.A.麦肯纳、Y.赤井、H.R.雅各布森、R.N.杜波依斯和M.D.布雷耶，《临床研究杂志》94:2504 - 2510,1994）。COX抑制剂的致畸性以及COX-2基因敲除小鼠的肾发育不全表明其在形态发生中起作用（J.E.丁丘克、B.D.卡尔、R.J.福赫特、J.J.约翰斯顿、B.D.贾菲、M.B.科温顿、N.R.康特尔、V.M.恩格、R.J.柯林斯、P.M.切尔尼亚克、A.G.斯图尔特和J.M.特拉斯科斯，《自然》378:406 - 409,1995；S.G.莫勒姆、R.拉根巴赫、C.D.洛夫廷、H.F.蒂亚诺、N.武洛马诺斯、J.C.詹内特、J.F.马勒、K.D.克拉克曼、A.莱德福德、C.A.李和O.史密斯ies。《细胞》83:473 - 482,1995）。发育中大鼠肾脏的印迹显示，COX-2 mRNA和免疫反应性蛋白在新生儿中存在，在出生后第2周和第3周达到峰值，并在第3个月降至成年水平。免疫定位和原位杂交在每个发育中的肾单位靠近致密斑的厚升支上皮细胞亚群中检测到强烈的COX-2免疫反应性和mRNA；2周后COX-2逐渐减弱。这些数据表明COX-2的表达受到正常的发育调控，并且可以在较长时间内维持；它们还支持这样的结论，即COX-2的代谢产物在哺乳动物肾单位的分化和早期功能中起重要作用。
