Tissue-Specific Expression of a Rat Renin Transcript Lacking the Coding Sequence for the Prefragment and Its Stimulation by Myocardial Infarction*

Abstract

An alternative transcript of the rat renin gene was recently characterized in the adrenal gland, in addition to the known messenger RNA (mRNA) coding for preprorenin. In the alternative transcript, exon 1 is replaced by exon 1A, a domain originating in intron 1. The reading frame of this mRNA, termed exon 1A-renin transcript, codes for a truncated prorenin that presumably remains intracellular, in contrast to preprorenin, which is targeted to the secretory pathway by its prefragment. We here demonstrate the tissue-specific regulation of expression of both transcripts by RT and PCR. In many tissues both transcripts are present, for example in the adrenal gland, spleen, liver, and hypothalamus. In some organs, however, only one of the renin mRNAs is found. In the kidney only the full-length mRNA coding for preprorenin is detected. In the heart exclusively the exon 1A-mRNA is expressed, but not the preprorenin transcript. After myocardial infarction, which is known to activate the intracardiac renin-angiotensin system, expression of exon 1A-renin mRNA in the left ventricle was stimulated about 4-fold, compared with that in sham-operated animals, whereas no mRNA corresponding to preprorenin was detectable. These findings may have implications for the current concepts of local extrarenal renin-angiotensin systems, as they provide the molecular basis for a possible intracellular function of renin and exclude a role for locally produced secretory renin in the heart.

Expression of a transcript encoding for cytosolic renin in the diseased human heart

“…In contrast we consistently detected renin-b in human hearts and thus conclude that this transcript is not brain-specific as previously suggested. These results are in agreement with our data in the rat [11].…”

“…In the rat we observed a specific upregulation of renin-b expression under various ischemia-related conditions. Thus, glucose depletion in cardiac cells in vitro and ligation of left coronary arteries in rats in vivo increased transcript levels of renin-b but not of secretory renin [11]. Therefore, we suggested that renin-b transcript levels are increased also in human heart diseases.…”

“…Therefore, we could only take advantage of animal models. In this respect we previously demonstrated that in ischemic heart disease specifically the transcript encoding for cytosolic renin was upregulated in rats [11] and that in cardiac rat cells ischemia-related conditions such as glucose depletion or combined anoxia with glucose depletion increased expression of cytosolic renin [12, 13, 35].…”

“…The alternative transcripts were described to be exclusively expressed in brain (renin-b) or lung (renin-c) [7, 9]. However, in rat we detected expression in many extrarenal tissues including the adrenal gland and heart [11]. In the rat heart, the expression of cytosolic renin but not of secretory renin was increased after myocardial infarction.…”

“…In the rat heart, the expression of cytosolic renin but not of secretory renin was increased after myocardial infarction. Furthermore, cells overexpressing cytosolic renin are more stable against necrotic cell death [10, 11], particularly under ischemic conditions such as glucose depletion and anoxia combined with glucose depletion [12, 13]. Also, overexpression of renin-b in the heart reduced the infarct size in Langendorff preparations ex vivo [12].…”