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2014 ; 4
(ä): 5967
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?2AP mediated myofibroblast formation and the development of renal fibrosis in
unilateral ureteral obstruction
#MMPMID25095732
Kanno Y
; Kawashita E
; Kokado A
; Kuretake H
; Ikeda K
; Okada K
; Seishima M
; Ueshima S
; Matsuo O
; Matsuno H
Sci Rep
2014[Aug]; 4
(ä): 5967
PMID25095732
show ga
Renal fibrosis is the final common pathway of a wide variety of chronic kidney
diseases. Myofibroblast formation via the differentiation of from tissue-resident
fibroblasts and bone marrow-derived mesenchymal stem cells (MSCs), and
epithelial-to-mesenchymal transition (EMT) is known to play a pivotal role in the
development of renal fibrosis. However, the detailed mechanisms underlying this
disorder remain unclear. We herein investigated the role of alpha 2-antiplasmin
(?2AP) in myofibroblast formation and the development of renal fibrosis. We
observed the development of renal fibrosis using unilateral ureteral obstruction
(UUO). ?2AP had accumulated in the UUO-induced obstructed kidneys and ?2AP
deficiency attenuated UUO-induced renal fibrosis in mice. The degree of
myofibroblast formation in the obstructed kidneys of ?2AP(-/-) mice was less than
that in ?2AP(+/+) mice. In vitro, ?2AP induced myofibroblast formation in renal
tubular epithelial cells (RTECs), renal fibrosblasts, and bone marrow-derived
mesenchymal stem cells (MSCs). ?2AP also induced the production of TGF-?, which
is known to be a key regulator of myofibroblast formation and fibrosis.
?2AP-induced the TGF-? production was significantly reduced by SP600125, c-Jun
N-terminal kinase (JNK) specific inhibitor. Our findings suggest that ?2AP
induces myofibroblast formation in the obstructed kidneys, and mediates the
development of renal fibrosis.