J Perinat Med. 2013 May;41(3):295-9. doi: 10.1515/jpm-2012-0178.
The study set out to investigate whether the osteopontin (OPN)-CD44-integrin-receptor-system is differently regulated during nephrogenesis in inborn nephron deficit, a major determinant of human primary hypertension and cardiovascular disease in adult life.
We compared a genetic rat model with an inherited nephron deficit, the Munich-Wistar-Froemter rat (MWF), to normotensive Wistar rats during nephrogenesis at day 19 of fetal development (E19) and at postpartal day 7 (D7).
Renal OPN mRNA (-75%, P<0.05) and protein expression (-38%, P<0.05) were strongly decreased at E19 in MWF compared to Wistar. Renal mRNA-expression of CD44 was increased at E19 in MWF (+271%, P<0.05). At D7, renal OPN protein expression was increased (+115%, P<0.05) and renal mRNA-expression of CD44 remained elevated compared to Wistar control (+127%, P<0.05).
Altered fetal expression of the OPN-CD44-integrin-receptor-system in the MWF model points to a possible role in low nephron number hypertension and cardiovascular disease.
本研究旨在探讨骨桥蛋白(OPN)-CD44-整合素受体系统在先天性肾单位缺陷(人类原发性高血压和成年期心血管疾病的主要决定因素)肾发生过程中的调控是否存在差异。
我们比较了一个具有遗传肾单位缺陷的基因大鼠模型,即慕尼黑-维斯塔-弗罗因特大鼠(MWF),与正常血压的 Wistar 大鼠在胚胎发育第 19 天(E19)和产后第 7 天(D7)期间的肾发生过程。
与 Wistar 相比,MWF 在 E19 时肾脏 OPN mRNA(-75%,P<0.05)和蛋白表达(-38%,P<0.05)明显降低。MWF 在 E19 时肾脏 CD44 mRNA 的表达增加(+271%,P<0.05)。在 D7 时,肾脏 OPN 蛋白表达增加(+115%,P<0.05),与 Wistar 对照组相比,肾脏 CD44 mRNA 的表达仍然升高(+127%,P<0.05)。
MWF 模型中 OPN-CD44-整合素受体系统在胎儿期表达的改变可能与低肾单位数高血压和心血管疾病有关。