Parathyroid hormone-related protein enhances insulin-like growth factor-I expression by fetal rat dermal fibroblasts

Interactions between cells of differing embryonic origins comprise a common theme during tissue development and repair. Often, communication between them can be mediated by soluble growth mediators and in some cases is restricted in focus. That is, some cells respond to, but do not produce, mediators expressed by other cells within the tissue. Because keratinocytes respond to but do not express insulin-like growth factor I (IGF-I), another skin cell population, the dermal fibroblast, may supply this factor. However, keratinocytes express, but do not respond to parathyroid hormone related protein (PTHrp), which increases cAMP production by dermal fibroblasts. Based on earlier results where inducers of cAMP increase local IGF-I expression in skeletal tissue, we postulated that PTHrp might induce local IGF-I by dermal fibroblasts and provide a source of this factor for keratinocyte activity. Our studies reveal that IGF-I mRNA and protein levels increase in response to PTHrp in vitro, and that this effect is replicated by inducers of cAMP, but not be activators of protein kinase C. Consequently, these factors appear to comprise a paracrine loop within the skin, permitting focused but restricted IGF-I expression to support skin growth, remodeling, or repair.