| First Author | Dou W | Year | 2005 |
| Journal | Am J Physiol Renal Physiol | Volume | 289 |
| Issue | 1 | Pages | F49-60 |
| PubMed ID | 15741608 | Mgi Jnum | J:104679 |
| Mgi Id | MGI:3612622 | Doi | 10.1152/ajprenal.00134.2004 |
| Citation | Dou W, et al. (2005) Defective expression of Tamm-Horsfall protein/uromodulin in COX-2-deficient mice increases their susceptibility to urinary tract infections. Am J Physiol Renal Physiol 289(1):F49-60 |
| abstractText | 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. |
