Investigation of Extracellular Matrix Protein Expression Dynamics Using Murine Models of Systemic Inflammation.

Abstract

Extracellular matrix (ECM) proteins form the structural support for migration of leukocytes and provide multiple signals to assist in their functions during inflammatory conditions. Presence of pro-inflammatory mediators in the tissues results in the remodelling of matrices which could modify the functions of extravasated leukocytes. Previous reports have shown changes in the expression of ECM proteins during local inflammatory responses. In this study, we have investigated the time- and tissue-specific expression profile of key ECM proteins in systemic inflammation using lipopolysaccharide (LPS)-induced endotoxemia and cecal ligation and puncture (CLP) mouse models. The results show that compared to naïve tissues, within 12h following CLP surgery, a 20-30-fold increase was observed in the expression of collagen-IV (Col-IV) transcripts in the mesentery tissues with a 2.4-fold increase in the protein by 24h. However, Western blot band intensities indicated that vimentin and fibrinogen were remarkably expressed in more quantity compared to Col-IV. Secondly, in CLP group of mice, fibrinogen showed 6-40-fold increase in mRNA level in various tissues with about 2-fold increase in the protein level compared to respective naïve tissues. Similar studies in the LPS-injected mice showed up to 2-3 fold increase in the expression of Col-IV, fibrinogen and vimentin at protein level in the lungs. In such animals, although similar pattern was observed for fibrinogen in kidney and liver tissues, the mesentery showed prominent changes in Col-IV and vimentin mRNA compared to CLP. Further, bioinformatics analysis showed multiple pathways which could be associated with vimentin, Col-IV and fibrinogen under inflammatory conditions both in human and mouse. The current study will help in better understanding of possible signalling from ECM proteins in inflammatory microenvironment and may contribute in development of cell adhesion-based therapeutics.