Storch S, Saggi S, Megyesi J, Price P M, Safirstein R
Department of Medicine, Mount Sinai School of Medicine, New York, New York.
Kidney Int. 1992 Jul;42(1):89-94. doi: 10.1038/ki.1992.265.
Northern and dot-blot analysis of polyadenylated RNAs of kidney cortical and outer medullary tissue was performed in male Sprague-Dawley rats at varying times up to 24 hours after bilateral ureteral obstruction (BUO), after 24 hours of unilateral obstruction (UUO) and at varying periods after release of BUO or UUO. Pre-proEGF (preproEGF) and Tamm-Horsfall (TH) mRNA declined by four hours of BUO to virtually undetectable levels at 24 hours of ureteral obstruction. Upon release of BUO or UUO, preproEGF and TH mRNA returned slowly toward normal but remained below control levels up to four days after release of ureteral obstruction. Urinary EGF excretion paralleled these changes in renal preproEGF mRNA. Although these changes are similar to those observed during nephrotoxic and ischemic renal failure, where the expression of the immediate early genes precedes the fall in preproEGF and TH expression, no such increase in the expression of these genes occurred after bilateral ureteral obstruction. These changes in preproEGF and TH expression could also be dissociated from uremia and high rates of DNA synthesis, suggesting that ureteral obstruction itself is a sufficient cause of the reduced expression. The increase in ureteral pressure and its functional and humoral effects may each play a role in reduced preproEGF and TH expression during ureteral obstruction.
在雄性斯普拉格-道利大鼠中,对双侧输尿管梗阻(BUO)后长达24小时的不同时间、单侧梗阻(UUO)24小时后以及BUO或UUO解除后的不同时间段,进行了肾皮质和外髓组织多聚腺苷酸化RNA的Northern印迹和斑点印迹分析。梗阻性肾病(BUO)4小时后,前表皮生长因子原(preproEGF)和Tamm-Horsfall(TH)mRNA下降,输尿管梗阻24小时时几乎检测不到。解除BUO或UUO后,preproEGF和TH mRNA缓慢恢复至正常水平,但在输尿管梗阻解除后4天内仍低于对照水平。尿表皮生长因子(EGF)排泄与肾preproEGF mRNA的这些变化平行。尽管这些变化与在肾毒性和缺血性肾衰竭期间观察到的变化相似,即立即早期基因的表达先于preproEGF和TH表达的下降,但双侧输尿管梗阻后这些基因的表达没有这种增加。preproEGF和TH表达的这些变化也与尿毒症和高DNA合成率无关,表明输尿管梗阻本身是表达降低的充分原因。输尿管压力的升高及其功能和体液效应可能各自在输尿管梗阻期间preproEGF和TH表达降低中起作用。