SilencingNLRC5 inhibits extracellular matrix ex pression in keloid
fibroblasts via inhibition of transforming growth factor-β1/Smad
Dermal fibrosis is characterized by collagen accumulation and hyperproliferation of fibroblasts.
NLRC5, as the largest member of nucleotide-binding domain and leucine-rich repeat (NLRs)
family, has recently been implicated in the development of hepatic fibrosis. However, the role of
NLRC5 in dermal fibrosis keloids remains unknown. Therefore, herein, we investigated the effects
of NLRC5 on keloid fibroblasts (KFs) and transforming growth factor-β1 (TGF-β1)-induced
collagen ex pression and explored the underlying mechanism. We observed that NLRC5 mRNA
and protein levels werehighly expressed in KFs, silencing NLRC5 greatly suppressed
TGF-β1-induced KFs proliferation. Silencing NLRC5also obviously inhibited the ex pression of
type I collagen, CTGF and α-smooth muscle actin (α-SMA) in human KFs induced by TGF-β1, as
well as the ex pression of TGF-β receptor I and II. Furthermore, silencing NLRC5 suppressed the
ex pression of TGF-β1-induced Smad2 and Smad3 phosphorylation in human KFs. Taken together,
our study suggest that silencing NLRC5 reducedECM ex pression in KFs through inhibiting the
TGF-β1/Smad signaling pathway. Therefore, NLRC5 may represent a promising target for
treatment of the keloid disease.