Gene regulation of MMPs and TIMPs by somatostatin in human fibroblasts

Abstract

Introduction:SST is a widespread neuropeptide with generally inhibitory function. The aim of this study is to evaluatethe effect of somatostatin in different concentrations on mRNA expression of MMPs and TIMPsin cultured, human, gingival fibroblasts. Methodology and resources: Human gingival fibroblasts were stimulated with 10-4, 10-9 or 10-12 M somatostatin DMEM without fetal calf serum; untreated fibroblasts served as controls. After incubation period, the RNA was extracted, and the first-strand cDNA was synthesized. Alterations in the expression of MMP-1, MMP-2, MMP-3, MMP-7, MMP-11, TIMP-1 and TIMP-2 mRNA were evaluated using real-time polymerase chain reaction (PCR). b-actin mRNA expression was used to normalize the data. Results: In 24 h treatment, SST, at the highest concentration induced a down-regulation on MMP-1, -2, -3 and -7 expression, and up-regulation on MMP-11 expression; while at the lowest concentration induced an up-regulation on MMP-1, -2, -3, TIMP-1 and -2 expression. At 72 hours treatment, similar effects were observed, except for the up-regulation on TIMP-2 at the higher SST concentration, an up-regulation on MMP-7 and -11 expression and a down-regulation on MMP-2 and TIMP-2 expression, at the lower SST concentration. Discussion:The modulation of inflammation by SST is still unclear. The findings of this work,suggests that it can modulate the gene expression of MMPs and TIMPs by cultured fibroblasts and its effects depend on the concentration. This may represent one of the mechanisms of inflammation suppression by SST.