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Loss of LAT1 sex-dependently delays recovery after caerulein-induced acute pancreatitis

World Journal of Gastroenterology 2022年第10期28卷 1024-1054页

作者： Cristina M Hagen Eva Roth Theresia Reding graf François Verrey rolf.graf Anurag Gupta Giovanni Pellegrini Nadège Poncet Simone Mafalda Rodrigues Camargo Institute of Physiology University of ZurichZurich 8057ZHSwitzerland Swiss Hepato-Pancreato-Biliary Center Department of Visceral and Transplantation SurgeryZurich University HospitalZurich 8091ZHSwitzerland Institute of Veterinary Pathology University of ZurichZurich 8057ZHSwitzerland

BACKGROUND The expression of amino acid transporters is known to vary during acute pancreatitis(AP)except for LAT1(slc7a5),the expression of which remains ***1 supports cell growth by importing leucine and thereby stimulates mammalian target of rapamycin(mTOR)activity,a phenomenon often observed in cancer *** mechanisms by which LAT1 influences physiological and pathophysiological processes and affects disease progression in the pancreas are not yet *** To evaluate the role of LAT1 in the development of and recovery from *** AP was induced with caerulein(cae)injections in female and male mice expressing LAT1 or after its knockout(LAT1 Cre/LoxP).The development of the initial AP injury and its recovery were followed for seven days after cae injections by daily measuring body weight,assessing microscopical tissue architecture,mRNA and protein expression,protein synthesis,and enzyme activity levels,as well as by testing the recruitment of immune cells by FACS and *** The initial injury,evaluated by measurements of plasma amylase,lipase,and trypsin activity,as well as the gene expression of dedifferentiation markers,did not differ between the ***,early metabolic adaptations that support regeneration at later stages were blunted in LAT1 knockout *** in females,we observed less mTOR reactivation and dysfunctional *** later regeneration phase was clearly delayed in female LAT1 knockout mice,which did not regain normal expression of the pancreas-specific differentiation markers recombining binding protein suppressor of hairless-like protein(rbpjl)and basic helixloop-helix family member A15(mist1).Amylase mRNA and protein levels remained lower,and,strikingly,female LAT1 knockout mice presented signs of fibrosis lasting until day *** contrast,pancreas morphology had returned to normal in wild-type *** LAT1 supports the regeneration of acinar cells after *** mice lacking LAT1 exh

关键词： Acute pancreatitis Amino acid transporter LAT1 Metabolism Regeneration Fibrosis

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