REGULATION OF TRANSCRIPTION BY THE RAT EGF GENE PROMOTER IN NORMAL AND ISCHEMIC MURINE KIDNEY-CELLS

Epidermal growth factor (EGF) is a small polypeptide belonging to a cl ass of molecules that can mediate cell growth, differentiation, and ac ute phase responses. EGF mRNA is transcribed primarily in cells of the salivary gland and the kidney. We have found that the tissue and cell ular specificities of EGF gene expression are controlled by a promoter region located upstream from the start of mRNA transcription. In a va riety of experimentally induced forms of acute renal failure, the mRNA and protein levels for kidney EGF fall markedly and remain low for a prolonged period. This decrease was determined by nuclear runoff trans cription to be a consequence of diminished transcription of the EGF ge ne rather than increased instability of the mRNA. Using transgenic mic e, we found the effect of renal ischemia on EGF mRNA transcription to be a result of a disease-mediated interruption of the function of this upstream promoter region, presumably from alterations in the activity of one or more cellular trans-acting factors.