Liver sinusoidal endothelial cells in hepatic fibrosis : Hepatology (original) (raw)

New Horizons

1Division of Gastrointestinal and Liver Disease and the USC Research Center for Liver DiseasesKeck Medicine of the University of Southern CaliforniaLos AngelesCA

*Address reprint requests to: Laurie D. DeLeve, M.D., Ph.D., Div. of GI/Liver, Keck Medicine of USC, 2011 Zonal Avenue‐HMR 603, Los Angeles, CA 90033. E‐mail: [email protected].

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Erratum

Abstract

Capillarization, lack of liver sinusoidal endothelial cell (LSEC) fenestration, and formation of an organized basement membrane not only precedes fibrosis, but is also permissive for hepatic stellate cell activation and fibrosis. Thus, dysregulation of the LSEC phenotype is a critical step in the fibrotic process. Both a vascular endothelial growth factor (VEGF)‐stimulated, nitric oxide (NO)‐independent pathway and a VEGF‐stimulated NO‐dependent pathway are necessary to maintain the differentiated LSEC phenotype. The NO‐dependent pathway is impaired in capillarization and activation of this pathway downstream from NO restores LSEC differentiation in vivo. Restoration of LSEC differentiation in vivo promotes HSC quiescence, enhances regression of fibrosis, and prevents progression of cirrhosis. (Hepatology 2015;61:1740–1746)

Erratum

In the May 2015 issue of Hepatology, in the New Horizons article titled “Liver Sinusoidal Endothelial Cells in Hepatic Fibrosis” (volume 61, pages 1740‐1746; doi: 10.1002/hep.27376), by Laurie D. DeLeve, the figure legends for Figs. 2 and 3 were switched.

The following legend should have printed with Fig. 2: “VEGF pathways in LSEC. Maintenance of the LSEC phenotype requires both the VEGF‐stimulated NO pathway working through soluble guanylate cyclase, cGMP, and protein kinase G and a VEGF pathway working independently of NO. The protein S‐nitrosylation pathway is not necessary to maintain the LSEC phenotype. LSEC, liver sinusoidal endothelial cell; NO, nitric oxide; sGC, soluble guanylate cyclase; VEGF, vascular endothelial growth factor.”

The following legend should have printed with Fig. 3: “The crosstalk of liver cells in regulating HSC quiescence and activation. In chronic liver injury, formation of apoptotic bodies, oxidative stress, and cytokines promote HSC activation. Differentiated LSECs function as a gatekeeper, preventing activation of the HSC. However, once the LSEC capillarizes, it no longer prevents HSC activation and permits or perhaps promotes activation of the HSC. LSEC capillarization can be reversed with an sGC activator that works downstream in the VEGF‐NO‐sGC pathway. Reversal of capillarized LSECs to differentiated LSECs promotes reversion of activated HSC to quiescence and induces some apoptosis of activated HSC. Hepatic macrophages in turn inhibit apoptosis of activated HSC. c LSEC, capillarized liver sinusoidal endothelial cell; d LSEC, differentiated liver sinusoidal endothelial cell; q HSC, quiescent hepatic stellate cell; NO, nitric oxide; sGC, soluble guanylate cyclase.”

We apologize for this error.

Hepatology. 62(1):326, July 2015.