Analysis of TGF-Mediated Synthesis of Extracellular Matrix Components

Coordinated regulation of production and turnover of extracellular matrix (ECM) components is essential for normal tissue homeostasis. The composition of the extracellular matrix can influence cell growth, state of differentiation, and specific gene induction. The multifunctional cytokine transforming growth factor-β (TGF-β) exerts its effects on cell proliferation, differentiation, and migration in part through its modulation of extracellular matrix components. TGF-β promotes net matrix deposition by increasing the expression of specific ECM components such as fibronectin (FN) and collagen, upregulating the expression of inhibitors of ECM proteases, such as plasminogen activator inhibitor-1 (PAI-1) and tissue inhibitors of matrix metaUoproteinases(TIMPs). while simultaneously suppressing the synthesis of proteases, which degrade matrix components, such as interstitial collagenase (reviewed in refs . 1 and 2 ). TGF-β also induces the expression of cell surface receptors for the ECM, the integrins, which enhance cell-matrix interactions (1 ,2 ).