Release of biologically active TGF-beta from airway smooth muscle cells induces autocrine synthesis of collagen

In severe or chronic asthma, there is an increase in airway smooth muscle c ell (ASMC) mass as well as an increase in connective tissue proteins in the smooth muscle layer of airways. Transforming growth factor-beta (TGF-beta) exists in three isoforms in mammals and is a potent regulator of connectiv e tissue protein synthesis. Using immunohistochemistry, we had previously d emonstrated that ASMCs contain large quantities of TGF-beta1-3. In this stu dy, we demonstrate that bovine ASMC-derived TGF-beta associates with the TG F-beta latency binding protein-1 (LTBP-1) expressed by the same cells. The TGF-beta associated with LTBP-1 localizes TGF-beta extracellularly. Further more, plasmin, a serine protease, regulates the secretion of a biologically active form of TGF-beta by ASMCs as well as the release of extracellular T GF-beta. The biologically active TGF-beta released by plasmin induces ASMCs to synthesize collagen I in an autocrine manner. The autocrine induction o f collagen expression by ASMCs may contribute to the irreversible fibrosis and remodeling seen in the airways of some asthmatics.