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2017 ; 2
(8
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Silencing SMOC2 ameliorates kidney fibrosis by inhibiting fibroblast to
myofibroblast transformation
#MMPMID28422762
Gerarduzzi C
; Kumar RK
; Trivedi P
; Ajay AK
; Iyer A
; Boswell S
; Hutchinson JN
; Waikar SS
; Vaidya VS
JCI Insight
2017[Apr]; 2
(8
): ä PMID28422762
show ga
Secreted modular calcium-binding protein 2 (SMOC2) belongs to the secreted
protein acidic and rich in cysteine (SPARC) family of matricellular proteins
whose members are known to modulate cell-matrix interactions. We report that
SMOC2 is upregulated in the kidney tubular epithelial cells of mice and humans
following fibrosis. Using genetically manipulated mice with SMOC2 overexpression
or knockdown, we show that SMOC2 is critically involved in the progression of
kidney fibrosis. Mechanistically, we found that SMOC2 activates a
fibroblast-to-myofibroblast transition (FMT) to stimulate stress fiber formation,
proliferation, migration, and extracellular matrix production. Furthermore, we
demonstrate that targeting SMOC2 by siRNA results in attenuation of
TGF?1-mediated FMT in vitro and an amelioration of kidney fibrosis in mice. These
findings implicate that SMOC2 is a key signaling molecule in the pathological
secretome of a damaged kidney and targeting SMOC2 offers a therapeutic strategy
for inhibiting FMT-mediated kidney fibrosis - an unmet medical need.