Expression of matrix metalloproteinase genes in regressing or remodeling organs during amphibian metamorphosis.

Several matrix metalloproteinases (MMP) are induced by thyroid hormone (TH) during the climax of amphibian metamorphosis and play a pivotal role in the remodeling of the intestine and the regressing tail and gills by degrading the extracellular matrix (ECM). We compared MMP gene expression levels precisely by quantitative real-time reverse transcription-polymerase chain reaction. The expression of MMP genes increases prominently at Nieuwkoop and Faber (NF) stages 60, 60-61 and 62 in the intestine, gills and tail, respectively, when the drastic morphological changes start in each organ. Gene expression analysis in the TH-treated tadpoles and cell line revealed that MMP mRNAs are upregulated in response to TH quickly within several hours to low levels and then increase in a day to high levels. All TH-induced MMP genes have TH response elements (TREs). The presence of high affinity TREs in MMP genes correlates with early TH-induction. Based on these results, we propose that TH stimulates the transcription of MMP genes through TREs within several hours to low levels and then brings about the main increase of mRNAs by TH-induced transcriptional factors, including TH receptor beta, in a cell type-specific transcriptional environment.