1Dept of Pharmacology and Toxicology, and 2University of Louisville Alcohol Research Center, University of Louisville, Louisville, KY USA
Fatty liver disease (e.g., ALD) follows a common natural history that leads to end-stage liver disease. Key events in fatty liver diseases include: chronic injury, impaired regeneration, and an increase in ECM deposition. The majority of research into the latter event in liver disease has focused on collagenous scar formation (i.e., fibrosis). However, the several ECM proteins accumulate rapidly in response to stress and may play key roles in hepatic damage. For example, Work by our group has demonstrated that fibrin ECM contributes to steatosis, inflammation and fibrosis in several models of experimental liver disease. It is becoming increasingly understood that the hepatic ECM responds dynamically to stress. The term “transitional tissue remodeling” describes qualitative and quantitative changes of matrix proteins occurring in response to injury that do not alter the overall architecture of the organ. The nature and magnitude of these changes to the ECM are currently poorly understood. Using proteomic approaches, we have characterizing the qualitative and quantitative changes to the ECM proteome (“matrisome”) in response to stress. Several ECM proteins responded generically to stress, whereas there are also proteins that respond uniquely to individual stresses. These results serve as a foundation for future analyses in hepatic models of liver disease, as well as a foundation for predictive modeling of the impact of these changes.