Faculty Collaboration Database

Defective expression of Tamm-Horsfall protein/uromodulin in COX-2-deficient mice increases their susceptibility to urinary tract infections. Am J Physiol Renal Physiol 2005 Jul;289(1):F49-60

Date

03/03/2005

Pubmed ID

15741608

DOI

10.1152/ajprenal.00134.2004

Scopus ID

2-s2.0-20844457162 (requires institutional sign-in at Scopus site)   25 Citations

Abstract

Mice lacking a functional cyclooxygenase-2 (COX-2) gene develop abnormal kidneys that contain hypoplastic glomeruli and reduced proximal tubular mass, and they often die of renal failure. A comparison of kidney-specific gene expression between wild-type and COX-2-deficient mice by cDNA microarrays revealed that although more than 500 mRNAs were differentially expressed between the two strains of mice depending on their ages, the genes encoding pre-pro-epidermal growth factor (pre-pro-EGF) and Tamm-Horsfall protein (THP)/uromodulin were aberrantly expressed in the kidneys of COX-2 -/- mice at all stages of their development. Downregulation of EGF could potentially affect renal development, and THP/uromodulin gene has been implicated in abnormal kidney development and end-stage renal failure in humans. We assessed in detail mechanism of defective THP/uromodulin gene expression and its potential consequences in COX-2-deficient mice. Consistent with the microarray data, the steady-state levels of THP/uromodulin mRNA were severely reduced in the COX-2 -/- kidney. Furthermore, reduced expression of renal THP/uromodulin, as assessed by Western blot and immunohistological methods, was closely corroborated by a corresponding decline in the urinary secretion of THP/uromodulin in COX-2 -/- mice. Finally, we demonstrate that the bladders of COX-2 -/- mice, in contrast to those of the wild-type mice, are highly susceptible to colonization by uropathogenic Escherichia coli.

Author List

Dou W, Thompson-Jaeger S, Laulederkind SJ, Becker JW, Montgomery J, Ruiz-Bustos E, Hasty DL, Ballou LR, Eastman PS, Srichai B, Breyer MD, Raghow R

Author

Stanley J. Laulederkind Research Scientist II in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Cyclooxygenase 2
Escherichia coli Infections
Female
Gene Expression Profiling
Gene Expression Regulation, Developmental
Genetic Predisposition to Disease
Kidney
Male
Mice
Mice, Knockout
Mucoproteins
Prostaglandin-Endoperoxide Synthases
Urinary Tract Infections
Uromodulin