3.7 | WISP-1 activates Hedgehog-Gli1 signaling in LF
fibroblasts
In order to elucidate the underlying mechanism by which elevated WISP-1
promoted LF fibrosis, we analyzed the effect of WISP-1 over-expression
and knockdown on the expression of Hedgehog signaling-related proteins,
including Gli1 and Shh, in LF cells from the LSCS patients. As a result,
we found that over-expression of WISP-1 increased the levels of Gli1 and
Shh in LF fibroblast, and knockdown of WISP-1 inhibited the expression
of Gli1 and Shh (Fig. 7 A and B). Consistent with these results,
recombinant human WISP-1 promoted Gli1 protein expression in a
dose-dependent manner in WISP-1-treated LF cells (Fig. 7C).
Furthermore, we used immunofluorescence staining to investigate Gli1
expression and nucleus translocation upon the effect of WISP-1. The
results revealed that Gli1 was preferentially distributed in the
cytoplasm rather than in the nucleus in the control group. However,
under the stimulation of WISP-1 over-expression, most Gli1 translocated
to the nucleus. Moreover, Gli1 translocation was inhibited in the WISP-1
knockdown LF cells (Fig. 7D), indicating that WISP-1 could activate the
Hedgehog-Gli1 pathway in LF fibroblasts.