Modulating hepatic macrophages with annexin A1 in non-alcoholic steatohepatitis

Abstract

Non-alcoholic steatohepatitis (NASH) and associated end-stage liver disease is a growing cause of concern throughout the Western world. It constitutes a significant clinical burden for which therapeutic approaches are very limited. Over the last years, considerable attention has therefore been paid to identifying potential therapeutic strategies to reduce this burden. Annexin A1 (AnxA1), a calcium-phospholipid binding protein, has been proposed to be a negative regulator of inflammation in the context of NASH. In a recent publication, Gadipudi, Ramavath, Provera et al. investigated the therapeutic potential of Annexin A1 treatment in preventing the progression of NASH. They demonstrate that treatment of mice with NASH with recombinant human AnxA1 can reduce inflammation and fibrosis without affecting steatosis or metabolic syndrome. This was proposed to be achieved through the modulation of the macrophage populations present in the liver. Here, we discuss the main findings of this work and raise some outstanding questions regarding the possible mechanisms involved and the functions of distinct macrophage populations in NASH.

Metabolic changes and propensity for inflammation, fibrosis, and cancer in livers of mice lacking lysosomal acid lipase

“…PLD3 and ANXA1 play important roles in the suppression of liver inflammation ( 48 , 49 ). Treatment of mice with recombinant ANXA1 reduces liver inflammation and fibrosis without affecting steatosis and metabolism ( 50 ), suggesting a possible mechanism by which Lal−/− mice attempt to combat liver inflammation. Conversely, upregulated expression of CHIL3 has been demonstrated to actively promote liver fibrogenesis ( 51 ).…”