Tenascin C (TNC) is a large homohexameric glycoprotein that is expressed by TM cells.
14 It is one of four members of the tenascin family of genes, which includes tenascins X, R, and W.
15 In other tissues, tenascins function to modulate cellular responses, cellular growth, adhesion, migration, and apoptosis.
15–19 Although they are highly expressed during embryonic development, both TNC and tenascin X (TNX) have much lower and restricted expression in adult tissues.
15,18–20 However, TNC is re-expressed in areas of tissue undergoing active ECM remodeling.
19 TNC binds other extracellular and cell-surface proteins including fibronectin, versican, integrins, and syndecans.
20 It is a modular domain protein composed of multiple fibronectin type III (FnIII) repeats and epidermal growth factor (EGF) domains. Complex alternative splicing introduces up to nine extra FnIII repeats, which are termed A1, A2, A3, A4, B, C, D, ad1, and ad2, between constitutively expressed FnIII repeats 5 and 6.
17 Transcripts including all combinations of these alternate domains exist, but these are expressed in a tissue- and cell-specific manner.
17 In porcine TM cells, two major
TNC splice forms were detected in approximately equal proportions: one containing no alternatively spliced domains and one containing FnIII repeat D.
21 Minor transcripts FnIII A1-B and FnIII B-D-6 were also detected, but transcripts containing FnIII A2, A3, A4, ad1, and ad2 were not detected by RT-PCR.
21 Moreover,
TNC transcription was increased and inclusion of FnIII domain D increased over time when TM cells were subjected to mechanical stretch.
21 Since mechanical stretch likely triggers the homeostatic response, this suggests that one mechanism by which TM cells reduce IOP is by increasing transcription of
TNC. This is consistent with its re-expression in areas of active remodeling in other tissues.