Hedgehog signaling is activated in human sclerodermatous cGVHD. Shh, Gli-1, and Gli-2 were detected by immunohistochemistry in skin biopsies of cGVHD patients and healthy volunteers. Fibroblasts were identified by staining with vimentin (n = 8 each). Representative examples of cGVHD patients and controls are shown at 1000-fold magnification. (A) Shh expression was strongly increased in cGVHD patients (Scl GVHD) compared with controls. (B-C) Gli-1 and Gli-2, both downstream transcription factor of the hedgehog pathway, accumulated in cGVHD patients with increased staining for Gli-1 (B) and Gli-2 (C), respectively, compared with controls.