Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stimulation of the zona glomerulosa phenotype by a low sodium diet is characterised by increased expression of aldosterone synthase accompanied by increases in (pro)renin, bFGF, c-fos and c-jun gene transcription. In contrast ACTH diminishes the specific glomerulosa phenotype. The EGF related transmembrane protein preadipocyte factor 1 (Pref-1) is specifically found in the zona glomerulosa and medulla of the adult rat adrenal as well as being expressed in fetal tissue. In addition the orphan nuclear receptor SF-1/Ad4bp considered to be an important factor in fetal adrenocortical development and differentiation may also have a role in zonal differentiation in the adult. To investigate their roles, adrenals were taken from adult Wistar rats maintained on a low sodium diet or ACTH treated (enhancing or diminishing zona glomerulosa function respectively) and compared with untreated controls. Localisation of Pref-1 was carried out by immunocytochemistry using the polyclonal antibody ZOG (anti Pref-1) and of SF-1 using a rabbit antiserum to SF-1. The experimental treatment resulted in a decrease and increase in Pref-1 expression in ACTH treated and low sodium diet treated rats respectively, in accordance with changes in abundance of glomerulosa cells. SF-1 expression was expected throughout the adrenal cortex, without zonal differentiation, though somewhat decreased by ACTH treatment. Of these two factors, only Pref-1 can be considered to have a role in zonal differentiation.
 ...
PMID:Pref-1, SF-1 and adrenocortical zonation. 988 10

A potent transcriptional enhancer was previously identified upstream of the mouse renin gene. Within the enhancer is a TGACCT direct-repeat motif, required for enhancer activity, that is the consensus sequence recognized by members of the thyroid hormone subfamily of steroid hormone receptors. We previously reported that RAR/RXR bind to this sequence and mediate the induction of renin promoter activity by retinoids. However, gel mobility shift assays clearly show that other as yet unidentified factors also bind to this motif. In order to identify some of these TGACCT binding factors, we screened a yeast one-hybrid cDNA library derived from mouse As4.1 cells. One of these encoded the orphan nuclear receptor Ear2. Recombinant Ear2 was purified from Escherichia coli and an antipeptide antisera was generated. EMSA showed that purified recombinant Ear2 specifically binds the TGACCT direct-repeat motif. Transfection assays showed that Ear2 potently decreases both baseline and retinoid-induced mouse renin promoter activity in a dose-dependent, enhancer-dependent, and sequence-specific manner. Mutations in Ear2, which abolish its binding to the TGACCT motif, also abolish transcriptional repression. Ear2 was identified as a nuclear protein in As4.1 cells, is one of the proteins binding to the TGACCT repeat motif, and its overexpression can repress transcription of the endogenous renin gene in As4.1 cells. These data suggest that Ear2 is a negative modulator of renin gene transcription in As4.1 cells, and that the renin enhancer may actually encode a complex positive and negative regulator of transcription.
 ...
PMID:Identification of a nuclear orphan receptor (Ear2) as a negative regulator of renin gene transcription. 1269 40

Estrogen-related receptor alpha (ERRalpha) is an orphan nuclear receptor highly expressed in the kidney, an organ playing a central role in blood pressure regulation through electrolyte homeostasis and the renin-angiotensin system. Physiological analysis revealed that, relative to wild-type mice, ERRalpha null mice are hypotensive despite significant hypernatremia, hypokalemia, and slight hyperreninemia. Using a combination of genome-wide location analysis and expression profiling, we demonstrate that ERRalpha regulates the expression of channels involved in renal Na(+) and K(+) handling (Scnn1a, Atp1a1, Atp1b1) and altered in Bartter syndrome (Bsnd, Kcnq1). In addition, ERRalpha regulates the expression of receptors implicated in the systemic regulation of blood pressure (Ghr, Gcgr, Lepr, Npy1r) and of genes within the renin-angiotensin pathway (Ren1, Agt, Ace2). Our study thus identifies ERRalpha as a pleiotropic regulator of renal control of blood pressure, renal Na(+)/K(+) homeostasis, and renin-angiotensin pathway and suggests that modulation of ERRalpha activity could represent a potential avenue for the management of hypertension.
 ...
PMID:Physiological genomics identifies estrogen-related receptor alpha as a regulator of renal sodium and potassium homeostasis and the renin-angiotensin pathway. 1990 Nov 97

This study aimed to investigate the possible involvement of the orphan nuclear receptor chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) in the regulation of renin gene expression. COUP-TFII colocalized with renin in the juxtaglomerular cells of the kidney, which are the main source of renin in vivo. Protein-DNA binding studies demonstrated that COUP-TFII binds to an imperfect direct repeat COUP-TFII recognition sequence (termed hereafter proxDR) in the proximal renin promoter. Because cAMP signaling plays a central role in the control of the renin gene expression, we suggested that COUP-TFII may modulate this cAMP effect. Accordingly, knockdown of COUP-TFII in the clonal renin-producing cell lines As4.1 and Calu-6 diminished the stimulation of the renin mRNA expression by cAMP agonists. In addition, the mutation of the proxDR element in renin promoter reporter gene constructs abrogated the inducibility by cAMP. The proxDR sequence was found to be necessary for the function of a proximal renin promoter cAMP-response element (CRE). Knockdown of COUP-TFII or cAMP-binding protein (CREB), which is the archetypal transcription factor binding to CRE, decreased the basal renin gene expression. However, the deficiency of COUP-TFII did not further diminish the renin expression when CREB was knocked down. In agreement with the cell culture studies, mutant mice deficient in COUP-TFII have lower renin expression than their control strain. Altogether our data show that COUP-TFII is involved in the control of renin gene expression.
 ...
PMID:Chicken ovalbumin upstream promoter transcription factor II regulates renin gene expression. 2264 48