Enteroendocrine cells are a potential source of serum autotaxin in men

Biochimica Et Biophysica Acta
Ruth BolierRonald P J Oude Elferink

Abstract

Serum autotaxin (ATX) activity is significantly increased in cholestatic patients. Our study aimed to unravel the source(s) of ATX in cholestasis. ATX activity and protein were measured in sera of healthy (n=33) and cholestatic patients (n=152), including women with intrahepatic cholestasis of pregnancy. ATX mRNA and protein expression were analyzed in various tissues from mice and men. Induction of ATX activity was assessed in mouse models of extrahepatic (bile duct ligation) and intrahepatic cholestasis (Atp8b1(G308V/G308V), 0.1% cholate-supplemented diet). ATX clearance in cholestatic and control mice was assessed after intravenous injection of recombinant ATX. Human hepatic clearance was estimated by comparing ATX activity in portal and hepatic vein serum. Serum ATX activity and ATX protein concentration tightly correlated under all conditions in patients and controls (p<0.0001). In humans Atx mRNA was highly expressed in small intestine, whereas in mice Atx was expressed mainly in brain and placenta but not in small intestine. Extensive ATX protein expression was identified in human, but not murine intestinal enteroendocrine cells. In murine models of cholestasis and cholestatic pregnancy plasma ATX activity was only mildl...Continue Reading

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Citations

Jun 22, 2018·American Journal of Physiology. Gastrointestinal and Liver Physiology·Rocio I R MaciasJose J G Marin
Nov 28, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Songbai LinC Chris Yun
Oct 28, 2019·Cancers·Eleanna KaffeVassilis Aidinis
Mar 2, 2019·Physiological Reports·Raphaëlle BourgeoisBenoit J Arsenault
Mar 19, 2021·Scientific Reports·Jacqueline LangedijkRonald Oude Elferink
Apr 2, 2021·Frontiers in Medicine·Jacqueline A G M LangedijkRonald P J Oude Elferink
Aug 15, 2021·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Jacqueline A G M LangedijkRonald Oude Elferink

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