SOX9 regulated matrix proteins are increased in patients serum and correlate with severity of liver fibrosis

Extracellular matrix (ECM) deposition and resultant scar play a major role in the pathogenesis and progression of liver fibrosis. Identifying core regulators of ECM deposition may lead to urgently needed diagnostic and therapetic strategies for the disease. The transcription factor Sex determining region Y box 9 (SOX9) is actively involved in scar formation and its prevalence in patients with liver fibrosis predicts progression. In this study, transcriptomic approaches of Sox9-abrogated myofibroblasts identified >30% of genes regulated by SOX9 relate to the ECM. Further scrutiny of these data identified a panel of highly expressed ECM proteins, including Osteopontin (OPN), Osteoactivin (GPNMB), Fibronectin (FN1), Osteonectin (SPARC) and Vimentin (VIM) as SOX9 targets amenable to assay in patient serum. In vivo all SOX-regulated targets were increased in human disease and mouse models of fibrosis and decreased following Sox9-loss in mice with parenchymal and biliary fibrosis. In patient serum samples, SOX9-regulated ECM proteins were altered in response to fibrosis severity, whereas comparison with established clinical biomarkers demonstrated superiority for OPN and VIM at detecting early stages of fibrosis. These data support SOX9 in the mechanisms underlying fibrosis and highlight SOX9 and its downstream targets as new measures to stratify patients with liver fibrosis

Stochastic Maximum Principle

International audienceThe stochastic maximum principle (SMP) gives some necessary conditions for optimality for a stochastic optimal control problem. We give a summary of well-known results concerning stochastic maximum principle in finite-dimensional state space as well as some recent developments in infinite-dimensional state space

A class of integration by parts formulae in stochastic analysis I

Consider a Stratonovich stochastic differential equation dxt = X(xt) ◦ dBt + A(xt)dt (1) with C ∞ coefficients on a compact Riemannian manifold M, with associate

SOME RELATIONS BETWEEN BOUNDED BELOW ELLIPTIC OPERATORS AND STOCHASTIC ANALYSIS

International audienceWe apply Malliavin Calculus tools to the case of a bounded below elliptic rightinvariant Pseudodifferential operators on a Lie group. We give examples of bounded below pseudodifferential elliptic operators on R d by using the theory of Poisson process and the Garding inequality. In the two cases, there is no stochastic processes besides because the considered semi-groups do not preserve positivity