Hepatic stellate cells regulate multiple aspects of hepatocyte function in health and disease

Abstract

Section snippets

Background and context

Hepatic stellate cells (HSCs) are best known as retinoid-containing cells in the space of Disse in healthy livers. In response to liver injury, they are activated, transdifferentiate into myofibroblasts and become the main scar-producing population in chronic liver disease (CLD). Much of the work on HSCs has focussed on their role in fibrogenesis, how they are activated and how they might be modulated or targeted to abrogate liver fibrosis.^1,2 However, the key roles HSCs play in other aspects

Objectives, methods and findings

In a recent article by Sugimoto et al. in Nature, the authors aimed to better characterise the functions of HSCs in controlling hepatocyte behaviour during health and disease.⁵ They used Lrat-cre mice crossed with iDTR (inducible diphtheria toxin receptor) mice, facilitating selective depletion of Lrat+ HSCs in vivo following administration of low dose diphtheria toxin. HSC depletion in healthy mice resulted in reduced liver size with less hepatocyte proliferation, consistent with previous

Significance of findings

This work highlights the complex role of HSCs in regulating hepatocyte behaviour, with highly context- and injury-dependent functional consequences. The most striking finding was the profound role of HSCs in controlling hepatocyte metabolic zonation across the entire liver lobule. Whilst Wnt signalling is well known to regulate zonation of the liver⁶ and RSPO3 expressed by pericentral endothelial cells has previously been shown to be essential for zone 3 hepatocyte functions,⁷ the key role of

Financial support

P.R. was funded by an MRC Senior Clinical Fellowship (MR/W015919/1).

Conflict of interest

The author of this paper declares that they do not have any conflict of interest.Please refer to the accompanying ICMJE disclosure forms for further details.