Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Velić, Ana; Hirsch, Jochen R.; Bartel, J; Thomas, Regina; Schröter, Rita; Stegemann, Heike; Edemir, Bayram; August, Christian; Schlatter, Eberhard; Gabriëls, Gert

doi:10.1097/01.asn.0000117287.74203.89

Cited by 22 publications

(39 citation statements)

References 47 publications

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“…5,6 The changes in expression levels of AQP2, ENaC, and NHE3 mRNA reported in this study confirmed our previously published observations. 5,6 In this study, we have observed an increased urinary volume and Na ϩ excretion within the first 4 d after aTX and massively disturbed urinary concentrating capacity of the graft compared with sTX, indicating that this functional deterioration is solely the result of rejection. Microarray analysis showed that genes with functions related to transport were over-represented in the list of genes downregulated after aTX (Figure 2).…”

Section: Discussionsupporting

confidence: 81%

“…5,6 When compared with the control group, the aTX model displayed signs of severe acute rejection characterized by massive leukocyte infiltration, as shown in Figure 1 and previously reported. 6 These changes were significantly reduced in kidneys of rats treated with CsA.…”

Section: Histologic and Functional Datamentioning

confidence: 57%

“…Renal TXs were performed as described previously. 5,6,35 For the present study, all recipients were bilaterally nephrectomized immediately before TX. For aTX and aTX ϩ CsA rats treated with CsA (5 mg/kg per d), kidneys of LBN rats (n ϭ 5) were transplanted into LEW rats.…”

Section: Kidney Transplantationmentioning

confidence: 99%

“…5,6 Twentyfour hours before TX surgery and at the endpoint, before kidney organ harvest, animals were housed in metabolic cages. Urine and blood samples were analyzed for protein (Bradford Blue, Bio-Rad Laboratories, München, Germany), creatinine (Enzym-Pap; Roche Diagnostics, Mannheim, Germany), and electrolytes by flame photometry (Instrumentation Laboratory 943, Kirchheim, Germany).…”

Section: General Functional Datamentioning

confidence: 99%

“…5,6 For example, the expression of Na ϩ /H ϩ -exchanger-3 (NHE3), aquaporin-2 (AQP2), and the epithelial Na ϩ channel (ENaC) were downregulated at the protein and mRNA level. Major transporters for water and Na ϩ reabsorption in the collecting duct (CD) are ENaC and AQP2.…”

Section: Introductionmentioning

confidence: 99%

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Acute Rejection Modulates Gene Expression in the Collecting Duct

Edemir

Reuter²,

Borgulya³

et al. 2008

Journal of the American Society of Nephrology

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Kidney transplantation, especially when associated with acute rejection, leads to changes in the expression of many genes, including those encoding solute transporters and water channels. In a rat model of acute rejection after allogeneic renal transplantation, impaired renal function, increased urine volume, and increased fractional excretion of sodium were observed. Gene array analysis revealed that these findings were associated with significant downregulation of water channels (aquaporin-1, -2, -3, and -4) and transporters of sodium, glucose, urea, and other solutes. In addition, changes in expression of various receptors, kinases, and phosphatases that modulate the expression or activity of renal transport systems were observed. Syngeneic transplantation or treatment with cyclosporine A following allogeneic transplantation did not impair graft function but did lead to the downregulation of aquaporin-1, -3, and -4 and several solute transporters. However, expression of aquaporin-2 and the epithelial sodium channel did not change, suggesting that the downregulation of these transporters following allogeneic transplantation is rejection-dependent. In conclusion, changes in gene expression may explain the impaired handling of solute and water after allogeneic transplantation, especially during acute rejection. Treatment with cyclosporine A improves the regulation of solute and water by preventing the downregulation of aquaporin-2 and epithelial sodium channel, even though many other transporter genes remain downregulated. Renal transplantation (TX) in humans is often accompanied by increased transport capacities of the graft and disturbances in salt and water homeostasis. 1-3 Half-life of grafts with normal function after TX is 11.5 yr compared with 7.2 yr for those with impaired renal function. 4 A better understanding of the underlying cellular and molecular mechanisms leading to such changes may help to increase longterm graft survival.Previously, using an allogeneic rat renal TX (aTX) model, we have demonstrated acute changes in expression and function of several transporters and receptors after aTX. 5,6 For example, the expression of Na ϩ /H ϩ -exchanger-3 (NHE3), aquaporin-2 (AQP2), and the epithelial Na ϩ channel (ENaC) were downregulated at the protein and mRNA level. Major transporters for water and Na ϩ reabsorption in the collecting duct (CD) are ENaC and AQP2. 7 The expression and activity of AQP2 are regulated by the antidiuretic hormone (vasopressin, AVP) via the G-protein coupled AVP-2 receptor (V2R). 8 The binding of AVP to the V2R leads to the activation of the G-protein Gs, followed by activation of adenylate cyclase (AC), increased cyclic adenosine monophosphate (cAMP) levels, activation of protein kinase A (PKA), and finally phosphorylation of AQP2 9 and translocation to the

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Section: Discussionsupporting

confidence: 81%

Section: Histologic and Functional Datamentioning

confidence: 57%

Section: Kidney Transplantationmentioning

confidence: 99%

Section: General Functional Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Acute Rejection Modulates Gene Expression in the Collecting Duct

Edemir

Reuter²,

Borgulya³

et al. 2008

Journal of the American Society of Nephrology

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NBCe1 Electrogenic Na+-Coupled HCO3 -(CO3 2-) Transporter

Kurtz¹

2016

Encyclopedia of Signaling Molecules

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NBCe1 Electrogenic Na+-Coupled HCO3−(CO32−) Transporter

Kurtz¹

2018

Encyclopedia of Signaling Molecules

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NBC2; NBC3; NBCn1; SLC4A7 Historical Background NBCn1 is an electroneutral Na + /HCO 3 À cotransporter encoded by SLC4A7 gene, a member of the bicarbonate transporter family of solute carrier 4 (SLC4). In total, this family contains ten members: (1) three electroneutral anion exchangers AE1 (SLC4A1), AE2 (SLC4A2), and AE3 (SLC4A3); (2) five Na + -coupled HCO 3 À transporters (NCBTs), including two electrogenic Na + /HCO 3 À cotransporters NBCe1 (SLC4A4), NBCe2 (SLC4A5), two electroneutral Na + /HCO 3 À cotransporters NBCn1 and NBCn2 (SLC4A10), and an electroneutral Na + -driven Cl À /HCO 3 À exchanger NDCBE (SLC4A8); (3) two less wellcharacterized members SLC4A9 and SLC4A11. The association between the transport of Na + and HCO 3 À was reported in 1970s in epithelial cells from different systems, such as proximal tubules (Burg and Green 1977) and jejunum (Turnberg et al. 1970; Podesta and Mettrick 1977). In 1983, Boron and Boulpaep clearly conceptualized for the first time Na + /HCO 3 À cotransporter based on their study with renal proximal tubules from Salamander (Boron and Boulpaep 1983). Proximal tubule is the major site for HCO 3 À reabsorption in the kidney. By microperfusion, Boron and Boulpaep demonstrated that the transport of HCO 3 À across the basolateral membrane of the proximal tubule is coupled to the transport of Na + . Moreover, this Na + -coupled transport of HCO 3 À is electrogenic and sensitive to inhibition by the stilbene disulfonate reagents, such as 4-acetamido-4isothiocyanostilbene-2,2'-disulfonic acid (SITS) and 4,4-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS).

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Renal Transplantation Modulates Expression and Function of Receptors and Transporters of Rat Proximal Tubules

Cited by 22 publications

References 47 publications

Acute Rejection Modulates Gene Expression in the Collecting Duct

Acute Rejection Modulates Gene Expression in the Collecting Duct

NBCe1 Electrogenic Na+-Coupled HCO3 -(CO3 2-) Transporter

NBCe1 Electrogenic Na+-Coupled HCO3−(CO32−) Transporter

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