Biology Reference
In-Depth Information
latter with alveogenesis. Elastin expression drops off rapidly after day P14 and
remains low throughout adulthood. Microfibrillar protein expression is more vari-
able throughout (Mariani et al.
2002
). Complicated patterns of gene expression
imply unique roles for these proteins during elastin fiber synthesis (Wagenseil
and Mecham
2007
). Finally, as implied above, elastin fibers may not only supply
a structural role but may be important in cellular organization. As noted,
Eln
/
mice displayed significant vascular structural abnormalities including subendothe-
lial cell proliferation and reorganization of smooth muscle prenatally. The lack of
inflammation and endothelial disruption implies that this is not just due to increased
strain in the arteries, but rather due to fundamental regulation of these cells by the
fibers. The mechanism is unknown, however (Li et al.
1998a
,
b
).
9.2.6.3 Role of Cells in Elastin Formation
Cells participate in the assembly of extracellular matrix components including
elastic fibers (Czirok et al.
2006
; Kozel et al.
2006
). Although the precise mechan-
isms are unclear, cells organize elastin aggregates into linear structures and deposit
them onto preexisting fibers. This aggregate formation is termed “microassembly.”
The transfer of these aggregates onto fibers is referred to as “macroassembly.” Both
these processes appear to involve cell movement. As the fiber grows, the motion
becomes more organized demonstrating the need for interaction and coordination of
multiple cells (Czirok et al.
2006
; Kozel et al.
2006
).
The mechanism by which cellular interaction occurs is unclear. Possible sites of
interaction include the elastin binding protein, integrins, and cell surface glycosa-
minoglycans (Hinek et al.
1988
; Rodgers and Weiss
2004
; Broekelmann et al.
2005
). Imaging studies utilizing fluorescently labeled antibodies showed that elas-
tin fiber formation occurred sequentially: fibronectin, fibrillin-1, MAGP1, fibulin-5,
and elastin fibers, whereby each fiber appears to replace or form in the location of
the preexisting fiber. Curiously, fibronectin is necessary for type I and type III
collagen matrix assembly, but not considered a component of the elastic fiber.
However, it may be essential for LOX processing from its proform to active form
(Kozel et al.
2006
).
9.2.6.4 Model of Elastic Fiber Assembly
Wagenseil and Mecham have proposed a hypothetical model of elastic fiber
assembly (Fig.
9.1
) based on the studies described above. The model uses a cell-
dependent method of assembly as observed with live imaging studies. Briefly,
tropoelastin is secreted by a cell (either smooth muscle or fibroblasts) and cross-
linked into aggregates on the cell surface via LOX. Fibulin-4 and/or -5 interacts
with the aggregates on the cell's surface to allow for optimal cross-linking and to
regulate the size of the aggregate. The cell continues to secrete and link tropoelastin
until the aggregate size is optimal. These aggregates are then transferred to a
