Differential effects of ureteral obstruction on rat kininogen gene family.
The precursors of kinins, K-kininogens and T-kininogens (KG), are encoded by separate genes that display 90% nucleotide sequence homology. Despite their homology, K-KG and T-KG genes are differentially regulated. The K-KG gene is expressed constitutively and encodes high- and low-molecular-weight KG, the precursors of the vasoactive nonapeptide bradykinin. In contrast, the T-KG gene is inducible, and its protein is a potent thiol-protease inhibitor. Given their potential role in the regulation of blood pressure, renal hemodynamics, and the response to inflammation and tissue injury, K-KG and T-KG gene expression in rats subjected to chronic (1 or 5 wk) unilateral ureteral obstruction (UUO), a maneuver that suppresses renal kallikrein synthesis to 25% of controls, has been examined. Northern and slot blots of total liver and kidney RNA were probed with oligonucleotides complementary to either T-KG or K-KG mRNA under high-stringency conditions. Steady-state levels of hepatic T-KG mRNA were increased in the UUO compared with sham-operated rats--2.7-fold at 1 wk and 4.1-fold at 5 wk (P < 0.05). Western blot analysis revealed that the 68-kd T-KG protein was up-regulated 2.5- to 3-fold in the liver of UUO rats (P < 0.05). In marked contrast, the abundance of high (2.3-kb)- and low (1.6-kb)-molecular-weight splicing transcripts of hepatic pre-K-KG mRNA was not altered at either time after UUO.(ABSTRACT TRUNCATED AT 250 WORDS)
el-Dahr
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Department of Pediatrics, Tulane University School of Medicine, New Orleans, LA 70112.
Dipp
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D000818:Animals; D001483:Base Sequence; D005786:Gene Expression Regulation; D015850:Interleukin-6 / Q000096:biosynthesis; D007704:Kininogens / Q000096:biosynthesis* / Q000145:classification / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018123:Receptors, Interleukin / Q000096:biosynthesis; D019947:Receptors, Interleukin-6; D013045:Species Specificity; D014517:Ureteral Obstruction / Q000235:genetics*
D015850:Interleukin-6; D007704:Kininogens; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6