TRANSCRIPTIONAL ALTERATIONS OF THE ENDOTHELIN-1 SYSTEM IN LUNG TISSUE OF OBESE ZUCKER RAT

Obesity has been implicated in the development of many carcinomas, and its prevalence is reaching epidemic proportions in children and teenagers. Recently the endothelin (ET) axis has been shown to have a role in the growth and progression of several tumour types including lung cancer. Aim of this study was to evaluate the ET-1 system transcriptional alterations in lung tissue of Zucker rats by Real Time-PCR subdivided in obese rats (O, n=20), and controls (CO, n=20): half were studied under fasting conditions (COfc-Ofc) and the remainders after the induction of acute hyperglycemia (COAH-OAH). Significantly higher prepro-ET-1 (p=0.05) and ECE-2 mRNA expression was observed in O with respect to CO. ECE-1 mRNA expression resulted undetectable in the lung tissue of zucker rats while ET-A and ET-B resulted to be expressed at similar levels both in CO than in O. The more relevant pathway observed subdividing into fasting and hyperglycemic rats are reported in Fig1. A significantly correlation was observed between ET-A and ET-B (p=0.04) as well as between prepro-ET-1 and ET-A (p=0.009). ET-1 overexpression, together with the ET-A and ET-B upregulation observed in OAH, are in line with previous studies on solid tumors. The study of ET axis may provide an important tool to modulate the inappropriate secretion of this peptide in pathological conditions providing the key to a new generation of chemotherapeutic agents.