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)

Swelling-activated Cl(-) currents (I(Cl,swell)) have been characterized in a mouse renal inner medullary collecting duct cell line (mIMCD-K2). Currents activated by exposing the cells to hypotonicity exhibited characteristic outward rectification and time- and voltage-dependent inactivation at positive potentials and showed an anion selectivity of I(-) > Br(-) > Cl(-) > Asp(-). NPPB (100 microm) inhibited the current in a voltage independent manner, as did exposure to 10 microm tamoxifen and 500 microm niflumic acid (NFA). In contrast, DIDS (100 microm) blocked the current with a characteristic voltage dependency. These characteristics of I(Cl, swell) in mIMCD-K2 cells are essentially identical to those of heterologously expressed cardiac CLC-3. A defining feature of CLC-3 is that activation of PKC by PDBu inhibits the conductance. In mIMCD-K2 cells preincubation with PDBu (100 nm) prevented the activation of I(Cl,swell) by hypotonicity. However, PDBu inhibition of I(Cl,swell) was reversed after PDBu withdrawal, but this was refractory to subsequent PDBu inhibition. Activation of either the cystic fibrosis transmembrane conductance regulator (CFTR) or Ca(2+) activated Cl(-) conductance (CaCC), which are coexpressed in mIMCD-K2 cells prior to PDBu treatment, abolished the PDBu inhibition of I(Cl,swell). Control of I(Cl,swell) by PKC therefore depends on the physiological status of the cell. In intact mIMCD-K2 layers in Ussing chambers, forskolin stimulation of an inward short-circuit current (due to transepithelial Cl(-) secretion via apical CFTR) was inhibited by cell swelling upon hypotonic exposure at the basolateral surface. Activation of I(Cl,swell) is therefore capable of regulating transepithelial Cl(-) secretion and suggests that I(Cl,swell) is located at the basolateral membrane. PDBu exposure prior to or during hypotonic challenge was ineffective in reversing the swelling-activated inhibition of Cl(-) secretion, but tamoxifen (100 microm) abolished the hypotonic inhibition of forskolin-stimulated short-circuit current (I(sc)). RT-PCR analysis confirmed expression of mRNA for members of the CLC family, including both CLC-2 and 3, in the mIMCD-K2 cell line.
 ...
PMID:The swelling-activated anion conductance in the mouse renal inner medullary collecting duct cell line mIMCD-K2. 1096 Jan 53

Bestrophin 1 (Best1) controls intracellular Ca(2+) concentration, induces Ca(2+)-activated Cl(-) conductance, and increases proliferation of colon carcinoma cells. Here, we show that expression of Best1 in mouse renal collecting duct (CD) cells causes i) an increase in cell proliferation, ii) a loss of amiloride-sensitive Na(+) absorption, iii) induction of Ca(2+)-dependent Cl(-) conductance (CaCC), and iv) epithelial-to-mesenchymal transition. During conditions of high proliferation or when we exposed CD cells to serum or TGF-beta1, we observed upregulation of Best1, increased CaCC, redistribution of the epithelial-to-mesenchymal transition marker beta-catenin, and upregulation of vimentin. In contrast, suppression of Best1 by RNAi inhibited proliferation, reduced CaCC, and downregulated markers of EMT. CaCC and expression of Best1 were independent of the cell cycle but clearly correlated to cell proliferation and cell density. During renal inflammation in LPS-treated mice or after unilateral ureteral obstruction, we observed transient upregulation of Best1. These data indicate that repression of cell proliferation, CaCC, and expression of Best1 occurs during mesenchymal-to-epithelial transition once CD cells polarize and terminally differentiate. These results may suggest a role for Best1 in renal fibrosis and tissue repair.
 ...
PMID:Bestrophin 1 promotes epithelial-to-mesenchymal transition of renal collecting duct cells. 1947 Jun 78