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2016 ; 7
(ä): 387
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Essential Role of Lyn in Fibrosis
#MMPMID27630579
Pham H
; Birtolo C
; Chheda C
; Yang W
; Rodriguez MD
; Liu ST
; Gugliotta G
; Lewis MS
; Cirulli V
; Pandol SJ
; Ptasznik A
Front Physiol
2016[]; 7
(ä): 387
PMID27630579
show ga
Fibrotic disorders involve replacement of normal parenchyma with myofibroblasts,
which deposit connective tissue, leading to obliteration of the function of the
underlying organ. The treatment options are inadequate and reflect the fact that
signaling targets in myofibroblasts are unknown. Here we identify the hyperactive
Lyn signaling in myofibroblasts of patients with chronic pancreatitis-induced
fibrosis. Lyn activation coexpress with markers of activated myofibroblasts, and
is increased ~11-fold in chronic pancreatitis compared to normal tissue.
Inhibition of Lyn with siRNA or INNO-406 leads to the substantial decrease of
migration and proliferation of human chronic pancreatitis myofibroblasts in
vitro, while leaving migration and proliferation of normal myofibroblasts only
slightly affected. Furthermore, inhibition of Lyn prevents synthesis of
procollagen and collagen in myofibroblasts in a mouse model of chronic
pancreatitis-induced fibrosis. We conclude that Lyn, as a positive regulator of
myofibroblast migration, proliferation, and collagen production, is a key target
for preventing fibrosis.