Role of TGF beta-mediated inflammation in cutaneous wound healing.

Among many molecules known to influence wound healing, transforming growth factor beta 1 (TGF beta 1) has the broadest spectrum of actions, affecting all cell types that are involved in all stages of wound healing. Both positive and negative effects of TGF beta 1 on wound healing have been reported. However, the underlying mechanisms are largely unknown.

Role of TGFbeta in skin inflammation and carcinogenesis.

The functions of transforming growth factor beta-1(TGFbeta1) are cell-context specific. We have found that TGFbeta1 expression in human skin squamous cell carcinoma (SCC) samples has two distinct distribution patterns: (1) either predominantly in suprabasal layers or (2) throughout tumor epithelia including basal proliferative cells. To understand whether the spatial TGFbeta1 expression patterns affect its functions, we have generated several keratinocyte-specific transgenic mouse models in which TGFbeta1 overexpression can be induced either predominantly in the suprabasal epidermis or in the basal layer of the epidermis and hair follicles.

Current view of the role of transforming growth factor beta 1 in skin carcinogenesis.

Previously, we have shown that transforming growth factor beta 1 (TGFbeta1) overexpression in suprabasal epidermis suppresses skin carcinogenesis at early stages, but promotes tumor invasion at later stages. To elucidate the role of TGFbeta1 overexpression in naturally occurring human squamous cell carcinomas (SCC), we screened TGFbeta1 expression patterns in human skin SCC samples and found that TGFbeta1 was overexpressed with two distinct patterns: either predominantly in suprabasal layers or throughout tumor epithelia including basal proliferative cells. To determine the effect of TGFbeta1 overexpression in basal keratinocytes, we generated transgenic mice expressing wild-type TGFbeta1 in basal keratinocytes and hair follicles using the K5 promoter (K5.