Alternatively spliced tenascin-C mRNA isoforms in human fetal membranes

Tenascin-C is an extracellular matrix glycoprotein whose monomers include eight consecutive fibronectin type III-like repeats, encoded by exons 10-16, and which are subject to alternative splicing. Transcripts containing these exons are expressed during tissue wounding and active tissue remodelling. Human fetal membranes have been proposed to undergo active tissue remodelling as part of the mechanisms leading to their rupture and immunoreactive tenascin-C has been detected in this tissue. Employing reverse transcription-polymerase chain reaction (RT-PCR) and exon-specific primers, products corresponding to multiple splicing events in the alternatively spliced region have now been identified. The overall splicing pattern would indicate that the major transcripts correspond to complete exclusion of the alternatively spliced region; inclusion of only exon 16; and inclusion of exons 10-14 and 16, including or excluding exon 12. The sole site in tenascin-C susceptible to cleavage by matrix metalloproteinases (MMP)-2 and MMP-3 is found within the exon 12 encoded repeat, therefore translation of isoforms which include or exclude exon 12 may produce 'large' tenascins mediating functions ascribed to this form but susceptible or resistant to these MMPs. The demonstration of expression of 'large' tenascin mRNA isoforms supports the concept that fetal membranes at term are a site of active tissue remodelling.