Background: Obesity is a complex pathology with interacting and confounding causes due to the environment, hormonal signalling patterns and genetic predispositions. It is an independent risk factor for cardiovascular disease, which can dramatically increase the likelihood of negative outcomes. Recently, obesity has been implicated in the development of many carcinomas, and its prevalence is reaching epidemic proportions in children and teenagers. 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 associated to the obesity in lung tissue of Zucker rats. Materials and Methods: Two groups of Zucker rats, 9-13 weeks, were studied: obese rats (O, n=20), and controls (CO, n=20). Half of them were studied under fasting conditions (CO fc -O fc ) and the remainders after the induction of acute hyperglycemia (CO AH -O AH ). The cDNA was synthesized with an iScript cDNA Synthesis kit (Bio-Rad, Hercules, CA, USA) using about 1 µg of total RNA as template. Real-Time PCR reactions were performed in duplicate in the Bio-Rad C1000(TM) thermal cycler (CFX-96). The experimental results were normalized with the three most stably expressed genes (YWHAG, SDHA, ACTB) Results: 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 and in O. When the two groups were further subdivided in fasting and hyperglycemic rats any significantly difference was not observed in the transcriptomic profile of ET-1 system between CO and O although O AH showed a more marked expression pathway than in all other groups. 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). Conclusion: ET-1 overexpression, together with the ET-A and ET-B upregulation observed in O AH , are in line with previous studies on solid tumors and suggest to evaluate, in the lung of these animals, the presence of any genomic damage. The study of ET axis and, in particular, ET receptor antagonism, 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.
TRANSCRIPTIONAL ALTERATIONS OF ET-1 SYSTEM IN LUNG TISSUE OF OBESE ZUCKER RAT.
Cabiati M;Caselli C;Prescimone T;Guiducci L;Giannessi D;Del Ry S
2014
Abstract
Background: Obesity is a complex pathology with interacting and confounding causes due to the environment, hormonal signalling patterns and genetic predispositions. It is an independent risk factor for cardiovascular disease, which can dramatically increase the likelihood of negative outcomes. Recently, obesity has been implicated in the development of many carcinomas, and its prevalence is reaching epidemic proportions in children and teenagers. 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 associated to the obesity in lung tissue of Zucker rats. Materials and Methods: Two groups of Zucker rats, 9-13 weeks, were studied: obese rats (O, n=20), and controls (CO, n=20). Half of them were studied under fasting conditions (CO fc -O fc ) and the remainders after the induction of acute hyperglycemia (CO AH -O AH ). The cDNA was synthesized with an iScript cDNA Synthesis kit (Bio-Rad, Hercules, CA, USA) using about 1 µg of total RNA as template. Real-Time PCR reactions were performed in duplicate in the Bio-Rad C1000(TM) thermal cycler (CFX-96). The experimental results were normalized with the three most stably expressed genes (YWHAG, SDHA, ACTB) Results: 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 and in O. When the two groups were further subdivided in fasting and hyperglycemic rats any significantly difference was not observed in the transcriptomic profile of ET-1 system between CO and O although O AH showed a more marked expression pathway than in all other groups. 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). Conclusion: ET-1 overexpression, together with the ET-A and ET-B upregulation observed in O AH , are in line with previous studies on solid tumors and suggest to evaluate, in the lung of these animals, the presence of any genomic damage. The study of ET axis and, in particular, ET receptor antagonism, 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
