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2014 ; 156
(3
): 548-55
Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue
growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells
in the liver
#MMPMID24882759
Charrier A
; Chen R
; Chen L
; Kemper S
; Hattori T
; Takigawa M
; Brigstock DR
Surgery
2014[Sep]; 156
(3
): 548-55
PMID24882759
show ga
BACKGROUND: Fibrogenic pathways in the liver are principally regulated by hepatic
stellate cells (HSC), which produce and respond to fibrotic mediators such as
connective tissue growth factor (CCN2). The aim of this study was to determine
whether CCN2 is shuttled between HSC in membranous nanovesicles, or "exosomes."
METHODS: Exosomes were incubated with HSC after isolation from conditioned medium
of control or CCN2-green fluorescent protein (GFP)-transfected primary mouse HSC
or human LX-2 HSC. Some exosomes were stained fluorescently with PKH26. HSC
co-culture experiments were performed in the presence of GW4869 exosome
inhibitor. CCN2 or CCN2-GFP were evaluated by quantitative real-time polymerase
chain reaction or Western blot. RESULTS: HSC-derived exosomes contained CCN2 or
CCN2 mRNA, each of which increased in concentration during HSC activation or
after transfection of HSC with CCN2-GFP. Exosomes, stained with either PKH26 or
purified from CCN2-GFP-transfected cells, were taken up by activated or quiescent
HSC resulting in CCN2-GFP delivery, as shown by their direct addition to
recipient cells or by the GW4869-dependency of donor HSC. CONCLUSION: CCN2 is
packaged into secreted, nano-sized exosomes that mediate its intercellular
transfer between HSC. Exosomal CCN2 may amplify or fine tune fibrogenic signaling
and, in conjunction with other exosome constituents, may have utility as a
noninvasive biomarker to assess hepatic fibrosis.