Type XII collagen, a member of the FACIT group, has been shown to
be present in chick,
6 29 mouse,
18 19 and
human corneas
8 and in several other dense connective
tissues in the adult.
18 19 24 Differential splicing of its
transcript gives rise to the short and long variant
forms.
2 24 38 The two forms have identical short signal
peptides at the N-terminus
3 followed by the alternatively
spliced NC3 domain and then identical COL 2, NC2, COL 1, and NC1
domains.
39 The NC3 domain of the long variant has several
subdomains, including 18 fibronectin type III repeats (FNIII), 4 von
Willebrand factor A (vWFa) complete repeats, and a
thrombospondin-terminal-like-domain.
22 38 39 The NC3
domain of the short form is shorter by approximately 1150 amino acids
and lacks 8 FNIII and 2 vWFa subdomains. Both forms have wider tissue
distribution during development, and they become more restricted in
certain adult tissues, such as the dense connective
tissues.
18 19 24 Although the short form is the more
predominant one in most tissues in the adult, we have shown that the
long form is the predominant form in the adult human
cornea.
8 The present study indicated that the same is the
case in the adult rabbit cornea. The significance of the differential
expression of these two forms during fetal development and in adult
tissues is not known. Based on the observation that type XII collagen
can promote collagen I gel contraction mediated by dermal fibroblasts,
Nishiyama et al.
30 has suggested that type XII collagen
may be involved in tissue compaction. Corneal stromal condensation
begins at the mid stages (between days 21 and 24) of corneal
development in the rabbit and proceeds from posterior to anterior
stroma.
40 41 The condensation pattern of the stromal
tissue coincided with the temporal and spatial distribution of the long
variant form of type XII collagen in the developing cornea. However,
the short form was expressed throughout the entire depth of the stroma
from very early stages of corneal development and was also expressed in
the sclera and the dermis of the eyelid. Thus, it may have a more
widespread function, such as the spacing of collagen fibrils and
prevention of fibril fusion in different tissues during development.
The type I collagen binding region is located at the carboxyl terminal
end of the molecule
26 and is, thus, present in both the
short and long forms. Recently, the short form has been shown to
interact with two proteoglycans, decorin and
fibromodulin.
42 The short form of type XII collagen may
act as a linking molecule between the collagen fibrils and decorin in
the interfibrillar space and, thus, may assist in regulating
interfibrillar matrix organization. Decorin is present not only in the
cornea but also in several other connective tissues,
43 and, therefore, the type I collagen–type XII collagen–decorin
interaction may be a widespread phenomenon in different tissues.