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2017 ; 14
(3
): 2568-2576
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Smad7-overexpressing rat BMSCs inhibit the fibrosis of hepatic stellate cells by
regulating the TGF-?1/Smad signaling pathway
#MMPMID28962196
Wu SP
; Yang Z
; Li FR
; Liu XD
; Chen HT
; Su DN
Exp Ther Med
2017[Sep]; 14
(3
): 2568-2576
PMID28962196
show ga
Mesenchymal stem cells (MSCs) are able to differentiate into hepatocytes, promote
the regeneration of hepatic cells and inhibit the progression of hepatic
fibrosis. Transforming growth factor (TGF)-?1 is one of the key factors in the
development of liver fibrosis, which also promotes extracellular matrix (ECM)
formation. Drosophila mothers against decapentaplegic 7 (Smad7) is an essential
negative regulator in the TGF-?1/Smad signaling pathway. In the present study,
bone mesenchymal stem cells (BMSCs) were isolated from rat bone marrow and
transfected with lentiviral vectors carrying the Smad7 gene. Smad7-enhanced green
fluorescent protein (EGFP)-BMSCs stably expressing Smad7 were subsequently
co-cultured with hepatic stellate cells (HSCs) for 48 h. Smad7 and TGF-?1 levels
in the culture medium were detected using ELISA, and the levels of collagen (Col)
I, Col III, laminin (LN) and hyaluronic acid (HA) were measured using
immunoassays. The early apoptosis rates of HSCs were determined via flow
cytometry. Reverse transcription-quantitative polymerase chain reaction and
western blotting were performed to evaluate the mRNA and protein expression
profiles, respectively. The results indicated that Smad7-EGFP-BMSCs stably
expressing Smad7 were successfully constructed. Upon co-culturing with rat
Smad7-EGFP-BMSCs, the early apoptotic rate of HSCs was significantly increased
(P<0.05). Levels of Smad7 in the culture medium were also significantly increased
(P<0.05), whereas the levels of TGF-?1, Col I, Col III, LN and HA were
significantly decreased (P<0.05). Furthermore, the mRNA and protein levels of
Smad7 and matrix metalloproteinase 1 were significantly increased (P<0.05),
whereas those of TGF-?1, ?-SMA, Smad2, smad3, TGF-? receptor I, Col I, tissue
inhibitors of metalloproteinase-1 and Col III were significantly decreased. The
results of the present study suggest that rat BMSCs overexpressing Smad7 may
inhibit the fibrosis of HSCs by regulating the TGF-?1/Smad signaling pathway.
This provides a novel insight into future treatments for liver fibrosis.