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2017 ; 40
(2
): 337-346
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Triptolide exerts protective effects against fibrosis following ileocolonic
anastomosis by mechanisms involving the miR-16-1/HSP70 pathway in IL-10-deficient
mice
#MMPMID28627592
Hou HW
; Wang JM
; Wang D
; Wu R
; Ji ZL
Int J Mol Med
2017[Aug]; 40
(2
): 337-346
PMID28627592
show ga
Surgeries, particularly ileocecal resection (ICR), are often required in the
treatment of Crohn's disease (CD). However, recurrences are common for patients
who undergo ICR, and anastomotic fibrosis is the main cause of re-operation. The
present study aimed to investigate the therapeutic effects of triptolide (TPL) in
ameliorating fibrosis following ileocolonic anastomosis. A model of IL?10?/? mice
undergoing ICR was used to study postsurgical inflammation and fibrosis of
anastomosis. For this purpsose, interleukin (IL)?10?/? mice were randomly divided
into 3 groups as follows: the control group, the saline?treated group subjected
to ICR (ST?ICR) and the TPL?treated group subjected to ICR (TT?ICR).
Wild?type (WT) mice of matching ages were assigned to the WT group. The effects
of TPL treatment on ileocolonic anastomosis were determined by histopathological
evaluation, western blot analysis and ELISA. The analysis of the effects of TPL
treatment on microRNA?16?1 (miR?16?1) and heat shock protein 70 (HSP70)
expression was carried out by RT?qPCR and western blot analysis. Compared with
the control group, significantly higher inflammation scores following anastomosis
were observed in the ST?ICR group (P<0.05), although reversion was observed in
the TT?ICR group, which was consistent with changes in the area of CD4+ cell
infiltration. The elevated fibrosis scores and the overexpression of
procollagen I and III in the ST?ICR group were all inhibited by TPL. With an
increase in the severity of inflammation and fibrosis, the levels of IL?6, tumor
necrosis factor?? (TNF??) and transforming growth factor??1 (TGF??1) increased;
however, a significant decrease in these levels was observed following treatment
with TPL (P<0.05). The results of RT?qPCR revealed that the upregulated miR?16?1
levels in the ST?ICR group were significantly reduced by TPL. HSP70, which can be
inhibited by miR-16-1, ameliorates anastomotic inflammation and fibrosis. Thus,
the present study demonstrates that TPL exerts a protective effect against
fibrosis following anastomosis in CD. The miR?16?1/HSP70 signaling pathway, which
can be regulated by TPL, may thus represent a novel therapeutic option in CD that
deserves further investigation.