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

Quantitative ligand binding autoradiography and in situ hybridization were employed to analyze [125I]insulin-like growth factor-I ([125I] IGF-I) and [125I]IGF-II-binding sites in human kidney sections. Binding sites for both ligands were concentrated in the inner medulla and glomeruli, with low levels present in the tubulo-interstitial cortex. Competition with cold IGF-I, IGF-II, and insulin was used to determine nonspecific binding and differentiate binding of ligands to the IGF-I and IGF-II receptors and IGF-binding proteins (IGFBPs). Nonspecific binding was less than 20% of the total for both ligands. Insulin (10(-5) mol/L), which binds to the IGF-I receptor, but not to the IGF-II receptor or IGFBPs, displaced 39 +/- 8% of [125I]IGF-I binding in glomeruli, 60 +/- 7% in the tubulo-interstitial cortex, and 32 +/- 7% in the medulla. Insulin produced no detectable decrease in [125I]IGF-II binding in any region. IGF-I (10(-8) mol/L), which binds strongly to IGFBPs, but not appreciably to the IGF-II receptor, produced reductions of 46 +/- 9%, 35 +/- 8%, and 39 +/- 12% in [125I]IGF-II binding in glomeruli, tubulo-interstitial cortex, and medulla, respectively. In situ hybridization showed that IGFBP-1-5 mRNAs were all expressed in glomeruli. IGFBP-2 mRNA was abundant in medullary collecting duct epithelium, whereas IGFBP-3, -4, and -5 mRNAs were localized in interstitial and vascular cells throughout the kidney. IGF-I and -II receptor mRNAs were widely distributed in renal epithelium. The abundance of local IGFBP gene expression was positively correlated with insulin-nondisplaceable IGF binding in specific kidney regions. In summary, [125I]IGF-I binding appears to be partitioned largely to IGFBPs in glomeruli and largely to the IGF-I receptor in the tubulo-interstitial cortex, with binding in the medulla more evenly divided. The proportion and regional distribution of [125I]IGF-II binding to IGFBPs are similar, but the balance appears to be primarily associated with the IGF-II, rather than the IGF-I, receptor. Finally, this study shows that [125I]IGF binding autoradiography combined with in situ hybridization can be used to localize and potentially quantitative expression of IGFBPs in tissue sections.
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PMID:Partition of insulin-like growth factor (IGF)-binding sites between the IGF-I and IGF-II receptors and IGF-binding proteins in the human kidney. 750 21

Immunocytochemistry, in situ hybridization, and radioimmunoassay were employed to examine the cellular distribution of mRNAs and proteins for IGF-I, II, IGF-II/M6P receptor, IGFBP2 as well as the levels of IGF-I and II in normal and unilaterally nephrectomized (Nx) adult rat kidneys. A similar distribution of immunoreactive IGF-I, and -II as well as IGF-II/M6P receptor was found in the principal cells of the cortical collecting duct and in all cells of the inner medullary collecting duct. In addition, immunostainable IGF-I and IGF-II/M6P receptor were noted in some inner medullary loops of Henle, while IGFBP2 was seen in the collecting ducts and loops of Henle of the inner medullar and the renal vasculature of all animals. By comparison, in situ hybridization revealed IGF-I mRNA only in the medullary thick ascending limbs while IGF-II mRNA was localized to the wall of the renal microvasculature in all kidneys. IGFBP2 mRNA was localized to the renal corpuscle and to inner medullary interstitial cells of all kidneys. These data suggest that renal IGF-I and IGFBP2 are synthesized at upstream sites along the nephron and then transported downstream for interaction with IGF receptors. Following nephrectomy, the renal levels of IGF-I peptide and mRNA were elevated at both 5 and 33 days post-nephrectomy, supporting a potential functional role for IGF-I in stimulating the structural and functional recovery in compensatory hypertrophy.
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PMID:Analysis of insulin-like growth factors (IGF)-I, and -II, type II IGF receptor and IGF-binding protein-2 mRNA and peptide levels in normal and nephrectomized rat kidney. 854 9