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lüll Enhanced expression of transforming growth factor-beta type I and type II receptors in wound granulation tissue and hypertrophic scar Schmid P; Itin P; Cherry G; Bi C; Cox DAAm J Pathol 1998[Feb]; 152 (2): 485-93In the present study we have analyzed and compared, by immunohistochemistry and in situ hybridization, the expression pattern of the R4/ALK5 transforming growth factor (TGF)-beta type I receptor (RI) and the TGF-beta type II receptor (RII) in normal human skin, in wounded skin at various stages during the transition of wound granulation tissue to scar, and in long-persisting post-burn hypertrophic scars. In normal human skin, expression of RI and RII was clearly visible in the epidermis, in epidermal appendages, and in vascular cells, although only a small number of dermal fibroblasts revealed detectable levels of TGF-beta receptor expression. In contrast, granulation tissue fibroblasts showed strong expression of both TGF-beta receptor types, although in normal-healing excisional wounds their density decreased during granulation tissue remodeling. However, in post-burn hypertrophic scars, RI- and RII-overexpressing fibroblasts were found in high densities up to 20 months after injury. From these findings we suggest that the repair process of deep wounds involves the transformation of a subset of fibroblastic cells toward an increased TGF-beta responsiveness and a transient accumulation of these cells at the wound site. In addition, our study provides evidence that excessive scarring is associated with a failure to eliminate TGF-beta receptor-overexpressing fibroblasts during granulation tissue remodeling, which leads to a persistent autocrine, positive feedback loop that results in over-production of matrix proteins and subsequent fibrosis.|Actins/metabolism[MESH]|Adolescent[MESH]|Adult[MESH]|Child[MESH]|Child, Preschool[MESH]|Cicatrix, Hypertrophic/*metabolism[MESH]|Female[MESH]|Granulation Tissue/*metabolism[MESH]|Humans[MESH]|Immunohistochemistry/methods[MESH]|Male[MESH]|Muscle, Smooth/metabolism[MESH]|RNA, Messenger/metabolism[MESH]|Receptors, Transforming Growth Factor beta/genetics/*metabolism[MESH]|Reference Values[MESH]|Wound Healing/*physiology[MESH] |