The liver matrisome - looking beyond collagens

Gavin E Arteel; Alexandra Naba

doi:10.1016/j.jhepr.2020.100115

The liver matrisome - looking beyond collagens

JHEP Rep. 2020 Apr 18;2(4):100115. doi: 10.1016/j.jhepr.2020.100115. eCollection 2020 Aug.

Authors

Gavin E Arteel^{1

2}, Alexandra Naba^{3

4}

Affiliations

¹ Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
² Pittsburgh Liver Research Center, Pittsburgh, PA, USA.
³ Department of Physiology and Biophysics, University of Illinois at Chicago, Chicago, IL, USA.
⁴ University of Illinois Cancer Center, Chicago, IL, USA.

Abstract

The extracellular matrix (ECM) is a diverse microenvironment that maintains bidirectional communication with surrounding cells to regulate cell and tissue homeostasis. The classical definition of the ECM has more recently been extended to include non-fibrillar proteins that either interact or are structurally affiliated with the ECM, termed the 'matrisome.' In addition to providing the structure and architectural support for cells and tissue, the matrisome serves as a reservoir for growth factors and cytokines, as well as a signaling hub via which cells can communicate with their environment and vice-versa. The matrisome is a master regulator of tissue homeostasis and organ function, which can dynamically and appropriately respond to any stress or injury. Failure to properly regulate these responses can lead to changes in the matrisome that are maladaptive. Hepatic fibrosis is a canonical example of ECM dyshomeostasis, leading to accumulation of predominantly collagenous ECM; indeed, hepatic fibrosis is considered almost synonymous with collagen accumulation. However, the qualitative and quantitative alterations of the hepatic matrisome during fibrosis are much more diverse than simple accumulation of collagens and occur long before fibrosis is histologically detected. A deeper understanding of the hepatic matrisome and its response to injury could yield new mechanistic insights into disease progression and regression, as well as potentially identify new biomarkers for both. In this review, we discuss the role of the ECM in liver diseases and look at new "omic" approaches to study this compartment.

Keywords: AUROC, area under the receiver operating characteristic curve; CCl4, carbon tetrachloride; ECM; ECM, extracellular matrix; Extracellular matrix; Fibrosis; HCC, hepatocellular carcinoma; Liver disease; MMP, matrix metalloproteinase; NAFLD, non-alcoholic fatty liver disease; NPV, negative predictive value; POSTN, periostin; PPV, positive predictive values; Proteomics; Regeneration; TGFβ, transforming growth factor beta.

Publication types

Review