Dual Role of PTP1B in the progression and reversión of non-alcoholic steatohepatitis

Abstract

Trabajo presentado en el EMBO Workshop: "Metabotic disorders and liver cancer", celebrado en Palma de Mallorca, del 23 al 26 de abril de 2017Background and aims: Non-alcoholic fatty river disease (NAFLD) is the most common chronic liver disease in western countries. protein tyrosine phosphatur" tn lrretn¡ negatively modulates insulin receptor-mediated signaling uld.i:. l therapeuiic targer for type 2 díauetls -i "L-".iiv.'w" ¡r"" evaluated the impact of prplB sl.age. deficiency r, non-utcJ¡oü" steatohepatitis (NASH), a severe NAFLD Materials PTPlB-deficient and Methods: Histological and molecurar characterization of livers from w,d-type and mice fed ctrow lcHo¡ or methionine/cholir"-a.n"r*, a-i"i iü"crJi.. ols" ',J""n, NASH recovery o model was established by switching MC¡ parenchymal i"ir.. s *""t9 ro érro r- )-z á"vr. N", liver cells (NpCs) were analyzed by flów "y,o-"try. (Jval mouse livers. prplB cells 1OCs.¡ were isolated liom and oCs markers were Áaryzed-in liveis from compared -i""'unJñasn pá,iir, ,ra to normal livers. Results: wild-type mice fed MCD for 8 weeks exhibited severe NASH with inñltration of NpCs and increased Fgf21' 116 and Illb mRNAs in.the river. rir.i" p*"."t"., retumed ro normal revers after swirching ro cHD. prplB deficiency accelerated MCD-ináíü Nasg."nected by liver histology and higher increases in NpCs infirtration and Fgf21 ur¿ uo PTPIB. -n¡a1. conversely, after switching to cHD, deficiencl Tpid]y improved liver hlistology and iar aeposition decreased earlier rhan in wild- type mice in parallel with higher cd36 and Cptla irRNe, *J ,'"-,o t.igrycerides, fatty ,rg!"rti;g i;."ur"a acid efflux from the liver. Recruitment of Nr* ""rl-urJi,rz ,ruó.-.ópr,ug. Á;¿?;";;?;;r" ,p- regulated in PTPlB-deficient compared to wild-type tive.s. inte.estingly, expression of oCs markers (Epcam and Cklg) increased r," MCD.in uotn genotypes. i,is'Lrrect being enhanced prplB-deficient livers' ocs lacking prplB dísplayed_ enhancJo p.áiir".u,i*' "apacity. In NASH parients, hepatic PTPTB mRNA levels conelated with OCs markers. - Conclusion: PTPIB elicits u, "ppit" role in NASH progression and regression and might modulate oval cells prolilerarion auring NAFLO progression.Peer reviewe