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)

To investigate regional aspects of hypoxic regulation of adrenomedullin (AM) in kidneys, we mapped the distribution of AM in the rat kidney after hypoxia (normobaric hypoxic hypoxia, carbon monoxide, and CoCl(2) for 6 h), anemia (hematocrit lowered by bleeding) and after global transient ischemia for 1 h (unilateral renal artery occlusion and reperfusion for 6 and 24 h) and segmental infarct (6 and 24 h). AM expression and localization was determined in normal human kidneys and in kidneys with arterial stenosis. Hypoxia stimulated AM mRNA expression significantly in rat inner medulla (CO 13 times, 8% O(2) 6 times, and CoCl(2) 8 times), followed by the outer medulla and cortex. AM mRNA level was significantly elevated in response to anemia and occlusion-reperfusion. Immunoreactive AM was associated with the thin limbs of Henle's loop, distal convoluted tubule, collecting ducts, papilla surface epithelium, and urothelium. AM labeling was prominent in the inner medulla after CO and in the outer medulla after occlusion-reperfusion. The infarct border zone was strongly labeled for AM. In cultured inner medullary collecting duct cells, AM mRNA was significantly increased by hypoxia. AM mRNA was equally distributed in human kidney and AM was localized as in the rat kidney. In human kidneys with artery stenosis, AM mRNA was not significantly enhanced compared with controls, but AM immunoreactivity was observed in tubules, vessels, and glomerular cells. In summary, AM expression was increased in the rat kidney in response to hypoxic and ischemic hypoxia in keeping with oxygen gradients. AM was widely distributed in the human kidney with arterial stenosis. AM may play a significant role to counteract hypoxia in the kidney.
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PMID:Expression of adrenomedullin in hypoxic and ischemic rat kidneys and human kidneys with arterial stenosis. 1471 86

We identified the inv gene that encodes left and right asymmetry and regulates kidney development based on the information of the inv mutant mouse. However, functional properties and the modulator of gene expression of inv have been unclear. We used the tissue injury model for assessing the functional roles of inv in ischemia reperfusion injury (IRI). The kidney tissue taken from rats with IRI showed reciprocal changes in mRNA expression of inv: a 0.25-fold decrease at 6 hours and then a gradual increase to a maximum 1.8-fold rise at 10 days of reperfusion. Next, oxidative stress was induced by exposing mouse inner medullary collecting duct (mIMCD-3) cells to hydrogen peroxide(H2O2) in the medium. Real-time PCR showed that mRNA expression of inv decreased 0.52-fold at 3 hours with 0.2 mM H2O2 in the medium, and then increased 3.1-fold at 24 hours with 0.1 mM H2O2 in the medium. RNA interference (RNAi) is a powerful tool to inhibit gene expression in experimental model systems. We knocked down inv gene expression in mIMCD-3 cells using RNAi to investigate the function of the inv gene. We designed a small interfering RNA (siRNA) to target the coding region of inv (inv-siRNA) and random-sequence scrambled siRNA(control siRNA). mIMCD-3 cells transfected with either the inv-siRNA or control siRNA were observed by microscopy. The cells transfected with inv-siRNA progressively lost cell-to-cell contact and the cell population significantly diminished approximately 48 hours post-transfection. The changes in gene expression profile were observed at time points (36 hours) using real-time PCR-based gene screening with categorized primer sets. Several genes related to structural protein of the matrix were downregulated. In contrast, repairing related genes were upregulated. In conclusion, gene expression of inv was modulated under oxidative stress and the inv gene may play a role in repairing and regenerating renal epithelial cells.
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PMID:[Functional analysis of the left-right determinant inv (inversion of embryonic turning) gene]. 1557 Aug 95

Induction of heme oxygenase-1 (HO-1) in renal tubules occurs as an adaptive and beneficial response in acute renal failure (ARF) following ischemia and nephrotoxins. Using an in vitro model of polarized Madin-Darby canine kidney (MDCK) epithelial cells, we examined apical and basolateral cell surface sensitivity to HO-1 induction by heme. Basolateral exposure to 5 microM hemin (heme chloride) resulted in higher HO-1 induction than did apical exposure. The peak induction of HO-1 by basolateral application of hemin occurred between 12 and 18 h of exposure and was dose dependent. Similar cell surface sensitivity to hemin-induced HO-1 expression was observed using a mouse cortical collecting duct cell line (94D cells). Hepatocyte growth factor (HGF) is known to decrease cell polarity of MDCK cells. Following pretreatment with HGF, apically applied hemin gave greater stimulation of HO-1 expression, whereas HGF alone did not induce HO-1. We also examined the effect of hypoxia on hemin-mediated HO-1 induction. MDCK cells were subjected to hypoxia (1% O(2)) for 24 h to simulate the effects of ischemic ARF. Under hypoxic conditions, both apical as well as basolateral surfaces of MDCK were more sensitive to HO-1 induction by hemin. Hypoxia alone did not induce HO-1 but appeared to potentiate both apical and basolateral sensitivity to hemin-mediated induction. These data demonstrate that the induction of HO-1 expression in polarized renal epithelia by heme is achieved primarily via basolateral exposure. However, under conditions of altered renal epithelial cell polarity and hypoxia, increased HO-1 induction occurs following apical exposure to heme.
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PMID:Epithelial cell polarity and hypoxia influence heme oxygenase-1 expression by heme in renal epithelial cells. 1662 74

Brain/kidney (B/K) protein is a novel double C2-like-domain protein that is highly expressed in rat brain and kidney, but its cellular localization and functional role in the kidney are still undetermined. We examined the cellular localization of B/K protein in the rat kidney under normal and ischemic conditions. Ischemia-reperfusion (I/R) injury was induced by clamping both renal arteries for 45 min, and animals were killed at 1 and 6 h and 1, 2, 3, 5, 7, 14, and 28 days after the reperfusion. Kidney tissues were processed for immunohistochemistry and immunoblot analyses using rabbit anti-B/K polyclonal antibodies. In control kidneys, B/K protein was expressed primarily in distal tubules including the thick ascending limb, distal convoluted and connecting tubules, and collecting duct. Notably, B/K protein was also expressed in the straight portion (S3 segment), but not in the S1 or S2, of proximal tubules, and podocytes of the glomerulus. In rat kidneys with I/R injury, expression of B/K protein was differentially regulated according to the anatomic location. In distal tubules, overall expression of B/K protein was markedly decreased. On the other hand, I/R injury significantly increased B/K protein expression in the S3 segment of the outer medulla as well as in the rat proximal tubular epithelial cell line NRK-52E in vitro. Furthermore, B/K protein was strongly expressed in many exfoliated cells in the lumen and urine. These findings suggest that B/K protein is closely associated with cell death in proximal tubules, which are vulnerable to I/R injury in the kidney.
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PMID:Differential regulation of B/K protein expression in proximal and distal tubules of rat kidneys with ischemia-reperfusion injury. 1689 91

Aquaporin-4 (AQP4) is a water-channel protein expressed strongly in the brain, predominantly in astrocyte foot processes at the borders between the brain parenchyma and major fluid compartments, including cerebrospinal fluid (CSF) and blood. This distribution suggests that AQP4 controls water fluxes into and out of the brain parenchyma. Experiments using AQP4-null mice provide strong evidence for AQP4 involvement in cerebral water balance. AQP4-null mice are protected from cellular (cytotoxic) brain edema produced by water intoxication, brain ischemia, or meningitis. However, AQP4 deletion aggravates vasogenic (fluid leak) brain edema produced by tumor, cortical freeze, intraparenchymal fluid infusion, or brain abscess. In cytotoxic edema, AQP4 deletion slows the rate of water entry into brain, whereas in vasogenic edema, AQP4 deletion reduces the rate of water outflow from brain parenchyma. AQP4 deletion also worsens obstructive hydrocephalus. Recently, AQP4 was also found to play a major role in processes unrelated to brain edema, including astrocyte migration and neuronal excitability. These findings suggest that modulation of AQP4 expression or function may be beneficial in several cerebral disorders, including hyponatremic brain edema, hydrocephalus, stroke, tumor, infection, epilepsy, and traumatic brain injury.
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PMID:Aquaporin-4 and brain edema. 1734 37

Acute renal injury induces metabolic acidosis, but its specific effects on the collecting duct, the primary site for urinary ammonia secretion, the primary component of net acid excretion, are incompletely understood. We induced ischemia-reperfusion (I/R) acute renal injury in Sprague-Dawley rats by clamping the renal pedicles bilaterally for 30 min followed by reperfusion for 6 h. Control rats underwent sham surgery without renal pedicle clamping. I/R injury decreased urinary ammonia excretion significantly but did not persistently alter urine volume, Na(+), K(+), or bicarbonate excretion. Histological examination demonstrated cellular damage in the outer and inner medullary collecting duct, as well as in the proximal tubule and the thick ascending limb of the loop of Henle. A subset of collecting duct cells were damaged and/or detached from the basement membrane; these cells were present predominantly in the outer medulla and were less frequent in the inner medulla. Immunohistochemistry identified that the damaged/detached cells were A-type intercalated cells, not principal cells. Both TdT-mediated dUTP nick-end labeling (TUNEL) staining and transmission electron microscopic examination demonstrated apoptosis but not necrosis. However, immunoreactivity for caspase-3 was observed in the proximal tubule, but not in collecting duct intercalated cells, suggesting that mechanism(s) of collecting duct intercalated cell apoptosis differ from those operative in the proximal tubule. We conclude that I/R injury decreases renal ammonia excretion and is associated with intercalated cell-specific detachment and apoptosis in the outer and inner medullary collecting duct. These effects likely contribute to the metabolic acidosis frequently observed in acute renal injury.
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PMID:Effects of ischemia-reperfusion injury on renal ammonia metabolism and the collecting duct. 1768 49

Apoptosis of tubular epithelial cells is a hallmark of acute kidney injury (AKI), but the cellular events preceding apoptosis in this setting are incompletely understood. Because matrix metalloproteinase 9 (MMP9) degrades matrix components involved in cell survival, we studied the role of MMP9 in AKI. In the mouse model of folic acid-induced AKI, we observed a marked increase of MMP9 activity in the S3 segment of the proximal tubule (S3PT), correlating with the apoptotic phase. MMP9 deficiency increased apoptosis and the severity of renal lesions and substantially delayed recovery of renal function. MMP9-/- mice exhibited significant apoptosis in the S3PT and the intercalated cells of the collecting duct (I-CD), whereas wild-type mice exhibited none in these segments. Stem cell factor (SCF), an MMP9 substrate, was identified in the S3PT, and its receptor, c-Kit, was expressed in both the S3PT and I-CD. MMP9 released the soluble form of SCF (sSCF) from kidney cells in vivo and in vitro. In addition, SCF inhibited apoptosis of tubular cells in vitro, rescued MMP9-/- S3PT and I-CD from apoptosis in vivo, and improved renal function. An ischemia-reperfusion model of AKI produced similar results. In patients with AKI, urinary sSCF increased with acute tubular necrosis but not with prerenal azotemia. In conclusion, these data show that MMP9 protects the S3 segment of the proximal tubule and the I-CD from apoptosis in AKI, most likely by releasing sSCF.
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PMID:MMP9 and SCF protect from apoptosis in acute kidney injury. 1932 63

The autacoid, adenosine, is present in the normoxic kidney and generated in the cytosol as well as at extracellular sites. The rate of adenosine formation is enhanced when the rate of ATP hydrolysis prevails over the rate of ATP synthesis during increased tubular transport work or during oxygen deficiency. Extracellular adenosine acts on adenosine receptor subtypes (A(1), A(2A), A(2B), and A(3)) in the cell membranes to affect vascular and tubular functions. Adenosine lowers glomerular filtration rate by constricting afferent arterioles, especially in superficial nephrons, and thus lowers the salt load and transport work of the kidney consistent with the concept of metabolic control of organ function. In contrast, it leads to vasodilation in the deep cortex and the semihypoxic medulla, and exerts differential effects on NaCl transport along the tubular and collecting duct system. These vascular and tubular effects point to a prominent role of adenosine and its receptors in the intrarenal metabolic regulation of kidney function, and, together with its role in inflammatory processes, form the basis for potential therapeutic approaches in radiocontrast media-induced acute renal failure, ischemia reperfusion injury, and in patients with cardiorenal failure.
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PMID:Adenosine receptors and the kidney. 1963 91

The epithelial cells that line the renal tubule are sometimes severely injured in the course of inflammatory kidney diseases. These renal tubule epithelial cells (RTECs) express some of the Toll-like receptors (TLRs) of the innate immune system. A number of studies have implicated RTECs, together with bone marrow-derived cells, in triggering an innate immune response to bacterial infection and/or ischemic stress. RTECs expressing TLR4, which recognizes lipopolysaccharide (LPS), contribute to defending the host against ascending urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPECs). Activation of TLR2 and TLR4 signaling by endogenous damage-associated molecular patterns controls the inflammatory responses of RTECs and cell apoptosis in kidneys subjected to ischemia/reperfusion (I/R) injury. This review will consider some recent advances in understanding of the role of RTECs in inducing the innate immune response in experimental models of ascending UTIs and renal I/R injury. Arginine vasopressin, which regulates renal water absorption, has been shown to act as a potent modulator of the innate response in collecting duct cells, a preferred intrarenal site for UPEC adhesion. The activation of the mitogen-associated protein kinase ERK1/2 in post-hypoxic RTECs has also been shown to be selectively regulated by TLR2 via the serine-threonine protein phosphatase 5, which is associated with the endoplasmic reticulum resident heat shock protein, gp96, which acts as a master chaperone of TLRs. These findings provide further support for the concept that RTECs are actively involved in triggering the innate immune response, at least in the context of ascending UTIs and I/R injury.
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PMID:Contribution of renal tubule epithelial cells in the innate immune response during renal bacterial infections and ischemia-reperfusion injury. 2058

Sickle cell disease (SCD), the first 'molecular disease' to be identified, has been well characterized as a single amino acid molecular disorder of hemoglobin leading to its pathological polymerization, with resulting red cell rigidity that causes poor microvascular blood flow, with consequent tissue ischemia and infarction. Thus, the manifestations of SCD chronic renal disease have long been considered clinical manifestations of an obstructive vasculopathy of the arterial and capillary microcirculation. Recently, accumulating evidence have indicated that blood vessel functions are affected by SCD, involving abnormal vascular tone and activated endothelium. These abnormalities are particularly prominent in the kidney where specific biochemical conditions in the medulla and papilla favor change in endothelial phenotype and in tubular phenotype that, in turn, may promote dysfunction and destruction of this organ through active endothelin (ET)-1 production and signals. High ET-1 urinary output in SCD subjects at steady state may reflect increased tubular activation of ET-1 production acting on the collecting duct thereby favoring the constant hyposthenuria. Chronically, augmented ET-1 concentrations in the SCD kidney would further aggravate ischemia and sickling through actions on vasa recta and red blood cells. The kidneys suffer multiple ischemic hits during SCD as consequences of vasos-occlusive crisis (VOC). Blockade of ET receptors unraveled the major vasoconstrictive role of ET-1 in the pathophysiology of VOC, stressing the pivotal role of abnormal endothelial phenotype in this hemoglobinopathy and opening potential new therapeutic options. At last, indirect evidence suggest that ET-1 may be involved in the progression of chronic glomerulosclerosis affecting a number of patients. In fact, sickle cell nephropathy is an emerging severe disease that requires pathophysiological studies and development of specific therapies.
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PMID:Endothelin in renal injury due to sickle cell disease. 2189 99


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