3.5 | Mechanical stretching stress induces WISP-1
expression in LF cells
Growing evidence has suggested that WISP-1 is involved in the process of
fibrosis in various organs (Sharma et al., 2010; Scotton et al., 2009).
In the previous study, we found that WISP-1 was markedly upregulated in
hypertrophic LF tissuse and highly associated with several
fibrosis-relevant factors, including collagen expression, LF thickness
and fibrosis score. As is known, mechanical stress is the main cause of
LF degeneration (Yoshiiwa et al., 2016; Fukui et al., 2015). Therefore,
we suspected that mechanical stress may be the cause resulted in he
abnormal expression of WISP-1 in hypertrophic LF tissuse and hereinafter
refer to the LF fibrosis. To ascertain this, we constructed an
experimental device in which repeated cyclic mechanical stretching
stimulation was applied to LF fibroblasts obtained from patients with
LSCS. The strength of the stretching stimulation was estimated from the
ratio of stimulation-induced cellular elongation to intrinsic cellular
size before stimulation. We examined whether WISP-1 mRNA levels were
increased by stretching stimulation
of 5% and
10% elongation for 24h. As expected,
WISP-1 mRNA expression in LF fibroblasts was markedly elevated by
stretching stimulation, and the increase in WISP-1 expression tended to
depend on the strength of the stretching stimulation (Figure 5A).
Furthermore, immunofluorescence staining indicated that the expression
of WISP-1 increased by 6h, 12h, and 24 h of mechnical stretching (10%
elongation, Figure 5B). Consistently, the levels of WISP-1 mRNA and
protein (Figure 5C) in LF cells were elevated in a time-dependent manner
under the action of mechanical stretching (10% elongation).