Deficiency of tPA selectively blocks the tubular epithelial-to-myofibroblast transition but not myofibroblastic activation from interstitial fibroblasts. Immunofluorescence staining demonstrates α-SMA–positive myofibroblasts in the obstructed kidneys in tPA^+/+ and tPA^–/– mice. Left column: staining with α-SMA (red); middle column: staining with renal proximal tubule marker, fluorescein-conjugated lectin from T. purpureas (green); right column: merging of the two images. (a, b, and c) Images taken 3 days after UUO in tPA^+/+ mice. (d, e, and f) Images taken 3 days after UUO in tPA^–/– mice. (g, h, and i) Images taken 7 days after UUO in tPA^+/+ mice. (j, k, and l) Images taken 7 days after UUO in tPA^–/– mice. No significant difference in the intensity and localization of α-SMA–positive cells in the obstructed kidneys at day 3 after UUO was observed between tPA^+/+ and tPA^–/– mice. Marked tubular epithelial-to-myofibroblast transition was evident in tPA^+/+ mice at 7 days after ureteral obstruction, as demonstrated by colocalization of α-SMA and tubular marker (yellow) (i). Myofibroblasts were reduced in number and limited to the interstitial compartment of the obstructed kidneys after 7 days in tPA^–/– mice (l). Scale bar, 20 μm.