IL10 inhibits starvation-induced autophagy in hypertrophic scar fibroblasts via
cross talk between the IL10-IL10R-STAT3 and IL10-AKT-mTOR pathways
#MMPMID26962683
Shi J
; Wang H
; Guan H
; Shi S
; Li Y
; Wu X
; Li N
; Yang C
; Bai X
; Cai W
; Yang F
; Wang X
; Su L
; Zheng Z
; Hu D
Cell Death Dis
2016[Mar]; 7
(3
): e2133
PMID26962683
show ga
Hypertrophic scar (HS) is a serious skin fibrotic disease characterized by
excessive hypercellularity and extracellular matrix (ECM) component deposition.
Autophagy is a tightly regulated physiological process essential for cellular
maintenance, differentiation, development, and homeostasis. Previous studies show
that IL10 has potential therapeutic benefits in terms of preventing and reducing
HS formation. However, no studies have examined IL10-mediated autophagy during
the pathological process of HS formation. Here, we examined the effect of IL10 on
starvation-induced autophagy and investigated the molecular mechanism underlying
IL10-mediated inhibition of autophagy in HS-derived fibroblasts (HSFs) under
starvation conditions. Immunostaining and PCR analysis revealed that a specific
component of the IL10 receptor, IL10 alpha-chain (IL10R?), is expressed in HSFs.
Transmission electron microscopy and western blot analysis revealed that IL10
inhibited starvation-induced autophagy and induced the expression of p-AKT and
p-STAT3 in HSFs in a dose-dependent manner. Blocking IL10R, p-AKT, p-mTOR, and
p-STAT3 using specific inhibitors (IL10RB, LY294002, rapamycin, and
cryptotanshinone, respectively) showed that IL10 inhibited autophagy via
IL10R?-mediated activation of STAT3 (the IL10R-STAT3 pathway) and by directly
activating the AKT-mTOR pathway. Notably, these results suggest that
IL10-mediated inhibition of autophagy is facilitated by the cross talk between
STAT3, AKT, and mTOR; in other words, the IL10-IL10R-STAT3 and IL10-AKT-mTOR
pathways. Finally, the results also indicate that mTOR-p70S6K is the molecule
upon which these two pathways converge to induce IL10-mediated inhibition of
autophagy in starved HSFs. In summary, the findings reported herein shed light on
the molecular mechanism underlying IL10-mediated inhibition of autophagy and
suggest that IL10 is a potential therapeutic agent for the treatment of HS.
free
free
free
