Ma C, Chegini N
Department of Obstetrics and Gynecology, University of Florida, Gainesville, FL 32610, USA.
Mol Hum Reprod. 1999 Oct;5(10):950-4. doi: 10.1093/molehr/5.10.950.
The objective of the present study was to determine whether transforming growth factor beta (TGF-beta) regulates the expression of matrix metalloproteinases (MMP) and the tissue inhibitor of MMP (TIMP) in myometrial smooth muscle 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 that TGF-beta1 (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 controls. In addition, TGF-beta1 slightly increased the production of TIMP-1, but not TIMP-2. Production of MMP-1 and MMP-3 was reduced by treatment with TGF-beta1, compared with the untreated control. A major portion of MMP-1 released into the culture-conditioned media was in complex with TIMP-1, and the levels of this complex were reduced by treatment with TGF-beta1. In conclusion, the data indicate that myometrial smooth muscle cells express MMP and TIMP mRNA and protein, and their expression is differentially regulated by TGF-beta1. Such a differential regulation of MMP and TIMP by TGF-beta may influence the rate of extracellular matrix (ECM) turnover following tissue injury, induced during myomectomy and Caesarean section, or in leiomyomas during growth.
本研究的目的是确定转化生长因子β（TGF-β）是否调节子宫肌层平滑肌细胞中基质金属蛋白酶（MMP）和MMP组织抑制剂（TIMP）的表达。利用人子宫肌层平滑肌细胞的原代培养物，我们发现这些细胞表达MMP-1、MMP-3、TIMP-1和TIMP-2的mRNA和蛋白，TIMP的值显著高于MMP。我们还发现，与未处理的对照相比，TGF-β1（1 ng/ml）增加了TIMP-1 mRNA的表达，同时降低了MMP-1和MMP-3 mRNA的表达。此外，TGF-β1略微增加了TIMP-1的产生，但未增加TIMP-2的产生。与未处理的对照相比，用TGF-β1处理后MMP-1和MMP-3的产生减少。释放到培养条件培养基中的大部分MMP-1与TIMP-1形成复合物，用TGF-β1处理后该复合物的水平降低。总之，数据表明子宫肌层平滑肌细胞表达MMP和TIMP的mRNA和蛋白，并且它们的表达受到TGF-β1的差异调节。TGF-β对MMP和TIMP的这种差异调节可能会影响在子宫肌瘤切除术、剖宫产或平滑肌瘤生长过程中诱导的组织损伤后细胞外基质（ECM）的周转速度。
