Effect of bone marrow mesenchymal stem cells on the TGF-β1/Smad signaling pathway of hepatic stellate

Abstract

ABSTRACT. This study investigated the effect of bone marrow mesenchymal stem cells (BMCs) on the transforming growth factor-β1 (TGF-b1)-induced activation of the Smad signaling pathway in rat hepatic stellate cells (HSCs). There were four experimental groups: 1) a blank control group, 2) a TGF-b1 treatment group, 3) an MSCcombined group, and 4) an induced MSC-combined group. Isolation and culture of rat liver HSCs in vitro and the proliferation of HSCs in each group were detected by MTT method. The expression of a-SMA and the TGF receptors (TbRI and II) were determined by immunohistochemical staining of HSCs in all groups, while Smad2/3, Smad4, and Smad7 mRNA expressions were detected by RT-PCR for HSCs in each group. TGF-b1 treatment significantly promoted the 8744-8754 (2015) proliferation of HSCs (P < 0.01); it has different inhibition effects on the proliferation of HSCs in the MSC-combined group and in the induced MSC-combined group (P < 0.05). TGF-β1 treatment also enhanced the expression of α-SMA as compared to the control group (P < 0.01). Alternatively, when compared with the pure TGF-β1 group, the MSCcombined group and the induced MSC-combined group showed lower α-SMA expression (P < 0.05). Activation of HSCs induced by TGF-b1, TβRI and TβRII fluorescence was (+ + +); the fluorescences of TbRI and TbRII in MSC-combined group and in induced MSC-combined group were (+ +) and (± ~ +), respectively. The expressions of TβRI and TβRII in activated HSCs induced by TGF-β1 were significantly decreased in the MSC-combined group (P < 0.05) and in the induced MSC-combined group (P < 0.01). The expression of HSC Smad2/3 and Smad4 was reduced in the MSC-combined group (P < 0.05) and in the induced MSC-combined group (P < 0.01), as compared to the TGF-b1 group. However, the expression of Smad7 in HSCs was upregulated in the MSC-combined group (P < 0.05) and in the induced MSCcombined group (P < 0.01). These results indicate that BMCs can inhibit the activation and proliferation of HSCs by downregulating the expression of TbRI and TbRII in the cell membrane of HSCs. Moreover, BMCs can upregulate the expression of Smad7 and downregulate the expression of Smad2/3 and Smad4 in the HSCs induced by TGF-b1, which resulted in an inhibition of HSC activation.

Stem Cell–Mediated Paracrine Signaling Alters Fibroplasia in Human Vocal Fold Fibroblasts in Vitro

“…28 However, MSC-mediated paracrine signaling stimulated cell proliferation and suppressed myofibroblast differentiation in skin fibroblasts, keratinocytes, hepatic stellate cells, and glomerular fibroblasts. 29-32 These previous reports concur with data from the current study.…”

Human umbilical cord mesenchymal stem cells facilitate the up‐regulation of miR‐153‐3p, whereby attenuating MGO‐induced peritoneal fibrosis in rats

“…TGF-b1 is involved in EMT processes and favours the formation of PF. 23 Hiwatashi et al 24,25 Previous study showed that peritoneal mesothelial cells could excrete various cytokines and growth factors, 27 and intraperitoneal transplantation of mesothelial cells was an effective way of attenuating peritoneal damage. 28 Foley-Comer et al 29 found that cultured and lavage-derived mesothelial cells had the ability to attach to the injured serosal surface, proliferate and became incorporated into the reconstituted mesothelium.…”

NADPH Oxidase Signaling Pathway Mediates Mesenchymal Stem Cell-Induced Inhibition of Hepatic Stellate Cell Activation

“…Multiple signaling pathways or channels have been confirmed to participate in the regulatory mechanism of hBM-MSCs on HSC activation [ 35 , 36 ], and our study may provide a new clue and possibility for explaining the protective effect of hBM-MSCs on liver fibrosis. The antifibrotic effects of the hBM-MSCs were also investigated by carbon tetrachloride- (CCl 4 -) induced liver fibrotic mouse model via the liver portal vein; the hBM-MSCs recover liver function markers at 21 days after transplantation.…”