Acute rejection modulates gene expression in the collecting duct.
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.
Edemir
Bayram
B
Medizinische Klinik und Poliklinik D, Experimentelle Nephrologie, Domagkstrasse 3a, 48149 Münster, Germany. edemir@uni-muenster.de
Reuter
Stefan
S
Borgulya
Reka
R
Schröter
Rita
R
Neugebauer
Ute
U
Gabriëls
Gert
G
Schlatter
Eberhard
E
D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051381:Rats
C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D007166:Immunosuppressive Agents; D016572:Cyclosporine