Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia.
Expression of parathyroid hormone-related protein in the rat glomerulus and tubule during recovery from renal ischemia.
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DOI：
10.1172/jci116905
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发表时间：
1993-12
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影响因子：
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通讯作者：
N. E. Soifer;S. V. Van Why;M B Ganz;M. Kashgarian;N J Siegel;A F Stewart
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文献类型：
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作者：
N. E. Soifer;S. V. Van Why;M B Ganz;M. Kashgarian;N J Siegel;A F Stewart
甲状旁腺激素相关蛋白（PTHrP）广泛表达于正常成人和胎儿组织中，其以自分泌/旁分泌方式起作用，刺激生长和分化，并具有早期反应基因特征。由于肾损伤的恢复与局部生长因子的释放有关，我们研究了PTHrP在正常和缺血成年大鼠肾脏中的表达和定位。雄性Sprague-Dawley大鼠双侧肾动脉完全阻断45 min，再灌注15 min，2、6、24、48和72 h。肾PTHrP mRNA水平，当与假手术动物相比，缺血后增加了两倍，并在6小时内达到峰值后再灌注。PTH受体、β-肌动蛋白和亲环素mRNA水平在缺血后均下降。PTHrP免疫组化染色强度增加，在近端肾小管细胞缺血后，改变其位置从弥漫性细胞质到近端的24小时后再灌注。此外，PTHrP定位于肾小球上皮细胞（内脏和壁），但不系膜细胞。在培养的系膜细胞中，PTHrP和PTH刺激增殖2 - 3倍。我们的结论是，PTHrP的mRNA和蛋白质的生产上调急性肾缺血性损伤后，PTHrP是存在于肾小球和近端和远端肾小管细胞，PTHrP刺激系膜细胞的DNA合成。PTHrP在正常和损伤肾脏中的确切功能仍有待确定。
Parathyroid hormone-related protein (PTHrP) is widely expressed in normal adult and fetal tissues, where it acts in an autocrine/paracrine fashion, stimulates growth and differentiation, and shares early response gene characteristics. Since recovery from renal injury is associated with release of local growth factors, we examined the expression and localization of PTHrP in normal and ischemic adult rat kidney. Male Sprague-Dawley rats underwent complete bilateral renal artery occlusion for 45 min, followed by reperfusion for 15 min, and 2, 6, 24, 48, and 72 h. Renal PTHrP mRNA levels, when compared with sham-operated animals, increased twofold after ischemia, and peaked within 6 h after reperfusion. PTH receptor, beta-actin, and cyclophilin mRNA levels all decreased after ischemia. PTHrP immunohistochemical staining intensity increased in proximal tubular cells after ischemia, changing its location from diffusely cytoplasmic to subapical by 24 h after reperfusion. In addition, PTHrP localized to glomerular epithelial cells (visceral and parietal), but not to mesangial cells. PTHrP and PTH stimulated proliferation two- to threefold in cultured mesangial cells. We conclude that PTHrP mRNA and protein production are upregulated after acute renal ischemic injury, that PTHrP is present in glomerulus and in both proximal and distal tubular cells, and that PTHrP stimulates DNA synthesis in mesangial cells. The precise functions of PTHrP in normal and injured kidney remain to be defined.