Acute Rejection Modulates Gene Expression in the Collecting Duct

• Published in: Journal of the American Society of Nephrology Vol. 19; no. 3; pp. 538 - 546
• Main Authors: EDEMIR, Bayram, REUTER, Stefan, BORGULYA, Reka, SCHRÖTER, Rita, NEUGEBAUER, Ute, GABRIËLS, Gert, SCHLATTER, Eberhard
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01.03.2008; American Society of Nephrology
• Subjects: Animals; Aquaporin 2 - metabolism; Basic Research; Biological and medical sciences; Cyclosporine - pharmacology; Gene Expression - drug effects; Gene Expression Profiling; Graft Rejection - metabolism; Graft Rejection - pathology; Immunosuppressive Agents - pharmacology; Kidney - pathology; Kidney Transplantation - adverse effects; Kidney Transplantation - pathology; Kidney Tubules, Collecting - metabolism; Medical sciences; Nephrology. Urinary tract diseases; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Rats; Rejection; Graft(material); Nephrology; Urinary system; Acute; Collecting duct; Gene expression; Kidney; Urology
• ISSN: 1046-6673; 1533-3450
• DOI: 10.1681/asn.2007040513

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.