Enhanced matrix metalloproteinase expression by Tisseel in mesothelial cells, normal peritoneal fibroblasts, and adhesion fibroblasts

Matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) are important in regulating tissue remodeling of extracellular matrix. Dysregulation of MMPs is considered to be important to postoperative adhesion development. To examine whether Tisseel, a fibrin sealant, exerts an effect on expression of MMPs from human peritoneal mesothelial cells, normal peritoneal fibroblasts, and adhesion fibroblasts, a tissue culture study was conducted for 6, 12, 24, and 48 h under normoxic conditions. A multiplex reverse transcriptase-polymerase chain reaction technique using β-actin as a housekeeping gene was used to determine relative change in MMP-1, MMP-2, and TIMP-1 mRNA levels under six conditions (five fibrin sealant preparations and a control). Our results demonstrate that MMP-1, MMP-2, and TIMP-1 are all expressed by human peritoneal mesothelial cells and fibroblasts. All fibrin sealant compositions increased MMP-1 mRNA levels by all cell types, although the time course and pattern varied. The fibrin sealant compositions had variable effects on MMP-2 mRNA expression. Interestingly, in mesothelial cells, TIMP-1 mRNA levels were reduced by fibrin-sealant-containing aprotinin at both concentrations, while being further reduced by fibrin sealant without aprotinin, particularly at 6 and 12 h. In adhesion fibroblasts, there was generally no effect, while in normal fibroblasts, expression of TIMP-1 increased after 24 h. These results suggest that fibrin sealant, in addition to assisting in the achievement of hemostasis, exerts biological effects on human peritoneal mesothelial cells and fibroblasts and modulates MMP expression. Thus, fibrin sealant may influence tissue remodeling and may thereby be able to alter postoperative adhesion development.