Regulation of matrix metalloproteinases (MMPs) and their tissue inhibitorsin human myometrial smooth muscle cells by TGF-beta 1

The objective of the present study was to determine whether transforming gr owth factor beta (TGF-beta) regulates the expression of matrix metalloprote inases (MMP) and the tissue inhibitor of MMP (TIMP) in myometrial smooth mu scle cells. Using primary cultures of human myometrial smooth muscle cells we found that these cells express MMP-1, MMP-3, TIMP-1 and TIMP-2 mRNA and protein, with significantly higher values of TIMP than MMP. We also found t hat TGF-beta 1 (1 ng/ml) increased the expression of TIMP-1 mRNA, while it reduced the expression of MMP-1 and MMP-3 mRNA, compared with untreated con trols. In addition, TGF-beta 1 slightly increased the production of TIMP-1, but not TIMP-2. Production of MMP-1 and MMP-3 was reduced by treatment wit h TGF-beta 1, compared with the untreated control. A major portion of MMP-1 released into the culture-conditioned media was in complex with TIMP-1, an d the levels of this complex were reduced by treatment with TGF-beta 1. In conclusion, the data indicate that myometrial smooth muscle cells express M MP and TIMP mRNA and protein, and their expression is differentially regula ted by TGF-beta 1. Such a differential regulation of MMP and TIMP by TGF-be ta may influence the rate of extracellular matrix (ECM) turnover following tissue injury, induced during myomectomy and Caesarean section, or in leiom yomas during growth.