There is accumulating evidence that polypeptide growth factors are elaborated by lung cells and are involved in pulmonary development and repair. Among these are the insulin-like growth factor I and II (IGF-I and IGF-II), peptides of about 7.5 KD having structural homology with insulin. Evidence that the IGFs have a role in the growth of lung includes the findings that IGFs, their receptors, and IGF binding proteins are expressed in lung cells, and that IGF-I stimulates the proliferation of lung cells. We hypothesize that (IGF-I) and (IGF-II) are important mediators of lung and tracheal development and repair, and promote growth by autocrine and/or paracrine mechanisms. We propose to examine the role of the IGFs in normal fetal and postnatal lung and tracheal development, and during the repair process after acute airway injury. We will focus on identifying the cells expressing IGFs and on the cell-cell interactions that we postulate result as a consequence of this expression. We will first determine expression of mRNAs, for the IGFs, their receptors and binding proteins in lung and trachea using Northern hybridization analyses and identify the cells expressing these mRNAs using in situ hybridization and histochemistry. The IGFs, IGF receptors and IGF binding proteins will then be localized in these tissues using immunocytochemistry. The actions of the IGFs in both growth and differentiation of lung and tracheal cells will be studied using cultured cells, cells transfected with IGF expression vectors, and IGF-I over- expressing and underexpressing transgenic mice. Finally, the role of IGFs in repair after airway injury will be examined using normal and transgenic animal models. The process of lung and tracheal development and repair are complex, involving many mechanisms. These studies should allow a clearer understanding of the role of the IGFs, their receptors and binding proteins in lung and trachea, and may also provide insights into developmental and repair functions of the IGFs in other organs.
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