Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (GH) and insulin-like growth factor I (IGF-I) exert a variety of actions in renal tissue. To shed light upon the renal GH-IGF I axis we have characterized the cell biology of GH and IGF I in two parts of the nephron that are targets for these peptides, proximal tubule and collecting duct. Receptors for both GH and IGF I are present in the basolateral membrane of the renal proximal tubular cell. GH activates phospholipase C and IGF I stimulates phosphorylation of its receptor at this site. Both peptides directly enhance gluconeogenesis in proximal tubule. GH stimulates IGF I gene expression in collecting duct. IGF I of collecting duct origin could act as a paracrine growth factor in other portions of the nephron. IGF I may be causative of renal hypertrophy that occurs in the settings of hypersomatotropism, unilateral nephrectomy (compensatory hypertrophy) and diabetes mellitus.
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PMID:Renal cellular biology of growth hormone and insulin-like growth factor I. 165 79

The renal collecting duct is a site of insulin-like growth factor I (IGF I) synthesis. Epidermal growth factor (EGF) is also synthesized within the kidney in the thick ascending limb of Henle's loop and the distal tubule. EGF has been shown to regulate IGF I expression in nonrenal tissues. To shed light upon a role of EGF in intrarenal regulation of IGF I gene expression, plasma membranes prepared from collecting ducts isolated from rat kidney and collecting ducts themselves were incubated in the presence and absence of recombinant human EGF (hEGF). hEGF enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for EGF signal transduction at this site. Inclusion of hEGF in suspensions of collecting ducts increased production of immunoreactive IGF I in a concentration-dependent manner. Production was stimulated significantly by addition of 10(-8) or 10(-6) M hEGF to suspensions for 2 h. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M hEGF in vitro. Our findings demonstrate a direct action of hEGF to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect an effect of EGF to stimulate IGF I production in the collecting duct of the intact kidney. Since EGF is produced in kidney, our findings are consistent with intrarenal paracrine regulation of IGF I gene expression by EGF.
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PMID:Insulin-like growth factor I gene expression in isolated rat renal collecting duct is stimulated by epidermal growth factor. 198 6

To determine whether growth hormone (GH) directly stimulates insulin-like growth factor I (IGF I) gene expression in renal collecting duct, plasma membranes prepared from collecting ducts isolated from rat kidney, and collecting ducts themselves were incubated in presence and absence of GH. GH enhanced phospholipase C activity in collecting duct plasma membranes establishing the potential for GH-signal transduction. Inclusion of GH in suspensions of collecting ducts increased production of immunoreactive IGF I in a time-dependent and concentration-dependent manner. Production was stimulated significantly by addition of 10(-10), 10(-8), or 10(-6) M GH to suspensions for 2 h. IGF I produced in isolated collecting ducts was released into the suspending media. Levels of IGF I mRNA in collecting ducts were increased 2.8-fold after incubation with 10(-6) M GH in vitro. IGF I of collecting duct origin was indistinguishable from recombinant human IGF I in terms of its size and receptor-binding characteristics. Our findings demonstrate a direct action of GH to enhance collecting duct IGF I gene expression in vitro. Such enhancement is likely to reflect the mechanism by which GH stimulates renal IGF I production in intact kidney.
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PMID:Growth hormone stimulates IGF I gene expression in isolated rat renal collecting duct. 239 72

We examined the regulation of insulin-like growth factor I (IGF-I) in kidney during the renal hypertrophy produced by two different experimental models: growth hormone treatment of hypophysectomized rats and compensatory hypertrophy subsequent to unilateral nephrectomy. Immunostaining for IGF-I in collecting ducts was enhanced in kidneys from growth hormone-repleted hypophysectomized rats, and the levels of IGF-I mRNAs were increased. In compensatory hypertrophy, no enhancement of the intensity of immunostaining was observed in kidneys of nephrectomized rats until 5 days postnephrectomy, at which time immunostainable IGF-I was increased markedly in medullary collecting ducts of hypertrophied kidneys compared with kidneys from sham-operated animals. No difference in steady-state levels of any IGF-I mRNA species was detected in whole kidneys or in collecting ducts from nephrectomized or sham-operated rats at any time postnephrectomy. Our findings demonstrate an increase in both IGF-I mRNA and in immunostainable IGF-I in collecting duct in the setting of growth hormone-induced renal hypertrophy but suggest that other, possibly translational, mechanisms underlie the induction of IGF-I synthesis during compensatory hypertrophy.
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PMID:Dual regulation of insulin-like growth factor I expression during renal hypertrophy. 254

Renal nephron segments are heterogeneous, and receptors for endothelin (ET)-1, ET-3, Angiotensin II (AII), epidermal growth factor (EGF), and insulin-like growth factor I distribute differently along the nephron segments. Recently, growth factors and vasoactive substances are reported to stimulate mitogen-activated protein kinase (MAP-K). In this study, we showed that mRNA and proteins of MEK-K, Raf-1-K, MAPK-K, MAP-K (p42 and p44), and S6-K are expressed ubiquitously in intact nephron segment. We demonstrated that four tiers of a cascade composed of the Raf-1-K, MAP-K, MAP-K, and S6-K are stimulated by ET-1 and ET-3 in rat intact glomeruli (Glm) via primarily B-type ET receptors and PKC. The stimulatory effect of EGF and IGF-I to MAP-K activity is inhibited by a tyrosine kinase inhibitor in Glm. IGF-I significantly stimulates MAP-K activity and EGF and All moderately stimulate MAP-K activity in the proximal convoluted tubule (PCT). EGF significantly increased MAP-K cascades and ET-1 and ET-3 slightly increased MAP-K cascades in the medullary thick ascending limb (MTAL). EGF significantly stimulated MAP-K cascades, and ET-1 and ET-3 moderately stimulate MAP-K cascades in the outer medullary collecting duct (OMCD) and the inner medullary collecting duct (IMCD). MAPK-K and S6-K are similarly stimulated by these agonists in each segment. This study shows that MAP-K cascades are expressed in every nephron segment. ET-1, ET-3, All, EGF, and IGF-I stimulate MAP-K cascades heterogeneously along the nephron segment. It was concluded that MAP-K cascades play an important role in the regulation of renal function.
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PMID:Presence and regulation of Raf-1-K (Kinase), MAPK-K, MAP-K, and S6-K in rat nephron segments. 874 82

The N-terminal sequence of a novel sheep-derived peptide with growth inhibitory activity has been obtained. The N-terminal fragment was chemically synthesised and designated EPL001. The kidney was chosen as the first mammalian system in which to study EPL001 since kidney growth can be accurately quantified following a surgical reduction in renal mass. Cell proliferation was measured in mouse collecting duct kidney (MCDK) cells stimulated with insulin-like growth factor I (IGF-I). Compensatory renal growth (CRG) was induced in Wistar rats and either EPL001 or an EPL001 antibody delivered by continuous renal tissue infusion. Mouse monoclonal antibodies to EPL001 were generated for immunoneutralisation, rabbit polyclonal antibodies were generated for immunohistochemistry. EPL001 had no apparent effect on IGF-I stimulated cell proliferation in MCDK cells in vitro, yet provoked a dose-dependent inhibition of CRG in vivo. An EPL001 antibody potentiated CRG, in the absence of exogenous EPL001, consistent with an inhibitory role in kidney growth for an endogenous peptide containing the EPL001 sequence. Tubular staining for epitopes to the EPL001 sequence was detected in normal human kidney sections and enhanced in renal cell carcinoma. Results support the presence of growth inhibitory activity in the N-terminus of a sheep-derived peptide with evidence for both its presence and endogenous activity in the kidney. Attempts to further characterise its structure and activity are ongoing.
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PMID:Inhibition of compensatory renal growth by the N-terminus of a sheep-derived peptide. 1902 30