Figure 9. Prominent co-localization of SMAD3 and p53 correlate with increased PAI-1 expression in the tubular epithelium of obstructed rat kidneys.
(A) Representative immunohistochemical images for SMAD3, p53, and PAI-1 localization in contralateral control (top) and obstructed UUO (bottom) rat kidneys. Nuclei were counterstained with hematoxylin. Arrows indicate tubular dilation while asterisks indicate interstitial expansion consistent with UUO-induced renal fibrosis. Contralateral kidneys without surgical manipulation served as control. (B) Heat maps of 24-hr TGF-β1-stimulated HK-2 tubular epithelial cells with or without Pifithrin-α pretreatment prior to analysis of mRNA transcripts using the TGF-β/BMP pathway PCR Array. Fold increase or decrease of gene expression is depicted as red and green, respectively. (C) Microarray results of selected target genes upregulated by TGF-β1 and sensitive to pifithrin-α pretreatment. Genes identified by PCR Array were classified as (D) TGF-β1Upregulated, p53 Sensitive Genes, (E) TGF-β1 Downregulated, p53 Sensitive Genes, and (F) TGF-β1 Upregulated, p53 Insensitive.