| First Author | López-Guisa JM | Year | 2011 |
| Journal | Am J Physiol Renal Physiol | Volume | 300 |
| Issue | 5 | Pages | F1244-54 |
| PubMed ID | 21270094 | Mgi Jnum | J:171476 |
| Mgi Id | MGI:4949998 | Doi | 10.1152/ajprenal.00701.2010 |
| Citation | Lopez-Guisa JM, et al. (2011) Vitronectin accumulates in the interstitium but minimally impacts fibrogenesis in experimental chronic kidney disease. Am J Physiol Renal Physiol 300(5):F1244-54 |
| abstractText | Vitronectin (Vtn) is a glycoprotein found in normal serum and pathological extracellular matrix. Given its known interactions with plasminogen activator inhibitor-1 (PAI-1) and Vtn cellular receptors, especially alphavbeta3 integrin and the urokinase receptor (uPAR), this study was designed to investigate its role in renal fibrogenesis in the mouse model of unilateral ureteral obstruction (UUO). Kidney Vtn mRNA levels were increased x1.8-5.1 and Vtn protein levels x1.9-3 on days 7, 14, and 21 after UUO compared with sham kidney levels. Groups of age-matched C57BL/6 wild-type (Vtn+/+) and Vtn-/- mice (n = 10-11/group) were killed 7, 14, or 21 days after UUO. Absence of Vtn resulted in the following significant differences, but only on day 14: fewer alphaSMA+ interstitial myofibroblasts (x0.53), lower procollagen III mRNA levels (x0.41), lower PAI-1 protein (x0.23), higher uPA activity (x1.1), and lower alphav protein (x0.32). The number of CD68+ macrophages did not differ between the genotypes. Despite these transient differences on day 14, the absence of Vtn had no effect on fibrosis severity based on both picrosirius red-positive interstitial area and total kidney collagen measured by the hydroxyproline assay. These findings suggest that despite significant interstitial Vtn deposition in the UUO model of chronic kidney disease, its fibrogenic role is either nonessential or redundant. These data are remarkable given Vtn's strong affinity for the potent fibrogenic molecule PAI-1. |
