Proteins that constitute acute phase response to tissue injury/in

Proteins that constitute acute phase response to tissue injury/infection and the complement cascade have also been explored as candidates involved in the inflammatory state present in fatty liver disease. In agreement with a previous report,36 we found that some serum acute phase proteins were significantly elevated in NASH compared to controls,

but found no changes in the expression levels of others. The same was observed with several proteins that comprise the complement system, which have been identified in previous proteomic studies as important diagnostic biomarkers for patients with cirrhosis and hepatocellular carcinoma.37, 38 Coagulation and development of liver fibrosis are tightly coupled and proteins that contribute to inflammation and immunity, production and remodeling of extracellular matrices, and cell proliferation, motility, selleckchem and survival are all involved in this process.39 Serum levels of most proteins involved in platelet aggregation and coagulation were elevated in NAFLD and NASH patients; however, circulating levels of

fibrinogen β chain and fibrinogen γ chain were significantly reduced. Interestingly, in the only other proteomics study using serum from NAFLD patients, Younossi et al.25 provisionally identified fibrinogen γ chain as one of the protein peaks that differed significantly among patient groups and controls. Taken together, these findings highlight the Volasertib importance of coagulation in the pathogenesis of NAFLD. Structural and extracellular matrix proteins also play a critical role in tissue remodeling and fibrosis in the liver,

and we observed significant changes in several of these proteins in NAFLD. Specifically, the expression of lumican, a protein involved in collagen 上海皓元医药股份有限公司 fibril assembly, was significantly elevated in the NASH F3/F4 group. This finding is consistent with the recent proteomics report by Charlton et al.26 in which they also demonstrated increased lumican messenger RNA (mRNA) and protein expression in liver tissue from patients with NAFLD and progressive NASH. The liver is the primary site of synthesis for most apolipoproteins and is responsible for the maintenance of lipoproteins and lipid metabolism.40–42 Serum apolipoprotein C1 and its precursor have been previously identified as potential biomarkers for patients with hepatitis C virus (HCV)-induced cirrhosis that progresses to HCV-induced hepatocellular carcinoma.37, 43 Similarly, we observed changes in the serum lipoprotein profile of patients with NAFLD and NASH. These findings may reflect the common observation of hypercholesterolemia and dyslipidemia in fatty liver disease. Finally, we observed a significant reduction in serum levels of proteins known to possess antiinflammatory and antioxidant capabilities, such as the high-density lipoprotein (HDL) particle-associated paraoxonase 1 and several apolipoproteins, in patients with NAFLD and NASH.

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