Connective Tissue Formation in Wound Healing - E-thesis

and negative elements within the first intron of COL1A1 have been identified (118). Cis-acting
DNA elements that direct high and tissue-specific transcription of the human COL1A2
promoter are comprised to the area about 350 nucleotides upstream of the transcriptional
initiation site (Fig. 5.). The constitutive activity of the human COL1A2 promoter is
demonstrated to be regulated equivalently by the three positive cis-acting elements and one
possible transcriptional repressor was found (108, 119, 120). TGF-β stimulation of human
COL1A2 promoter is mediated by a multiprotein complex that interacts with two distinct
promoter segments termed TGF-β-response element (TbRE). Transcription factors which bind
to this complex have been identified (105, 106). Putative regulatory elements controlling
human COL3A1 gene has been found; a TATA consensus element and two potential
transcription factor binding sites (78). The promoter of the human COL5A1 is shown to have a
number of features characteristic of the promoters of “house-keeping “ and growth controlrelated
genes in that it is GC-rich. It lacks obvious TATA and CAAT boxes and has multiple
transcription start sites. A minimal promoter region of COL5A1 gene is shown to contain a
number of binding sites for several transcription factors (111) (Fig. 5.). The shortest DNA
sequence capable of directing high and cell type-specific transcription from the human
COL5A2 gene include a TATA-like element and two positive regulatory sequences (81, 113)
(Fig. 5.). Trans-acting factors binding to one of these elements are indentified and
combinatorial interactions among these factors may involve in regulating tissue-specific
production of type V collagen (112).
Post-transcriptional mechanisms involve the mRNA stability and mRNA splicing. A highly
conserved sequence is found around the translation initiation site in the three collagen mRNAs,
proα1(I), proα2(I) and proα1(III) (70, 115, 121). This region of the collagen mRNAs contains
an inverted repeat sequence with the potential for forming an intramolecular 5’-stem-loop
structure (115, 122). This region provides a potential mechanism for translational regulation.
The stem-loop has been shown to decrease type I collagen mRNA stability and so to inhibit
translation (123) and it has been suggested to be involved in the regulation of feedback
translational repression by N- and C-terminal propeptides (122). Translational repression of
pro-collagen mRNAs by N-terminal and C-terminal propeptides play significant role in the
control of collagen biosynthesis. Intact N-terminal propeptide of either type I or type III procollagen
could selectively inhibit pro-collagen biosynthesis by human fibroblasts and the C-
terminal propeptide of the human α2(I) pro-collagen chain inhibits both collagen and
fibronectin synthesis by human fibroblasts (124, 125). Stability of most mRNAs is determined
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