The liver plays key roles in fighting infection, extracting energy from food, ridding the body of waste and other important functions. Although a healthy liver successfully performs these numerous jobs every day, it can be harmed when exposed to additional, repeated insults, such as alcohol misuse. Long-term, continuous damage to the liver leads to scarring of the tissue (fibrosis) and ultimately liver failure. In fact, liver disease is the fifth most common cause of death in the UK.

Fibrotic extracellular matrix // Image by Adam Byron

Fibrosis is a wound healing response that results in the uncontrolled accumulation of extracellular matrix (ECM), the proteins and polysaccharides that surround cells in tissues and organs. The ECM environment is an important regulator of cellular function and fate. To gain insight into changes in the ECM upon fibrosis, work by Tamir Rashid, Jon Humphries and others sought to define the composition of fibrotic liver ECM. The paper (on which I am a co-author) has been published in the current issue of the Journal of Proteome Research.

The study biochemically isolated the ECM from liver cells that produce excessive ECM during fibrosis and compared this to non-fibrotic ECM. Mass spectrometry–based proteomics, an approach to analyse all proteins in a sample, was used to catalogue the proteins present in the ECM samples. The analyses validated the vast majority of known fibrotic liver ECM components, but also discovered a large number of putative novel components up-regulated in fibrotic ECM.

Two novel proteins, CYR61 and Wnt-5a, were validated in fibrotic liver tissue by immunohistochemistry, a method for detecting proteins in tissues using antibodies. With further evaluation, these molecules have the potential to be biomarkers that could indicate the progression of liver disease. Elucidating how these molecules function in fibrotic ECM will also advance our understanding of the mechanisms underlying fibrosis, which could lead to the identification of new drug treatments.

The paper is freely available as an ACS AuthorChoice article, and the datasets are also available as a resource to aid further study of the composition of fibrotic ECM.

Funding: This work was supported by the Wellcome Trust and the National Institute for Health Research.

Citation: ST Rashid, JD Humphries, A Byron, A Dhar, JA Askari, JN Selley, D Knight, RD Goldin, M Thursz, MJ Humphries, Proteomic analysis of extracellular matrix from the hepatic stellate cell line LX-2 identifies CYR61 and Wnt-5a as novel constituents of fibrotic liver. J. Proteome Res. 11, 4052-4064 (2012). DOI | PMID | Full text | Reprint