TISSUE POLARITY GENE FRIZZLED IS EXPRESSED IN THE INTERSTITIAL MYOFIBROBLASTS IN A RENAL FIBROSIS.

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Interstitial fibrosis is the final event of many chronic renal diseases, and the presence of myofibroblast is critical in the process. Presence of myofibroblasts (a-smooth muscle actin positive, αSMA+) is confined to a large extent to the vascular smooth muscle cells of normal kidneys but extends to the tubulointerstitium and periglomerular space in the development of fibrosis. The mechanisms that control the myofibroblast localization are unknown, but are likely to involve the transmission of polarity signals. Possible candidate genes for this control are the rat homologues of the Drosophila polarity gene frizzled. In Drosophila, the frizzled gene controls the polarity of the wing hair growth. In mammalians, two highly homologous genes (fri and fz2) have been identified. The aims of the present study were to localize and to quantify the expression of fz2 in rat kidney in the course of unilateral ureteral obstruction, in order to study their putative role in the spatial control of myofibroblast localization in interstitial fibrosis. Immunohistochemistry for αSMA and in situ hybridization for the frizzled gene fz2 are performed on serial sections at 1, 2, 3 and 5 weeks after ureteral obstruction as well as normal kidney. Gradual increase in the number of αSMA+ cells in interstitium was demonstrated from week 1 to week 5.There was no fz2+ myofibroblast in normal kidney, however it appeared in the interstitium from week 1. The peak of the number of fz2+ myofibroblast in the interstitium was shown at week 3 and it decreased at week 5 when the expansion of interstitial fibrosis was demonstrated. In conclusion, myofibroblasts express a homologue of Drosophila tissue polarity gene frizzled (fz2) and fz2 expression in myofibroblasts is involved in the spatial control of the early phase of interstitial fibrosis in a unilateral ureteral obstruction model.