Hepatocyte growth factor‐induced differentiation of bone mesenchymal stem cells toward hepatocyte‐like cells occurs through nuclear factor‐kappa B signaling in vitro

Yang, Tongxi; Wang, Yi; Jiang, Shasha; Liu, Xiaoping; Yu, Zhongjie

doi:10.1002/cbin.10630

Cited by 7 publications

(8 citation statements)

References 24 publications

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“…This idea is supported by the upregulation of miR-7 in the HGF-treated MCF-10A cells, and by the strong association between miR-7 and HGF expression in normal mammary tissues. There have also been previous studies indicating the tumor-suppressive activity of HGF by abrogating the oncogenic effects of c-Myc during early stages of liver carcinogenesis 46 , as well as enhancing the differentiation activity in mammary glands 14 and hepatocytes 13 . Therefore, during tumorigenesis, upregulated HGF would drive the expression of oncogenes, while in normal cells, miR-7 would mediate HGF to downregulate the same oncogenes.…”

Section: Discussionmentioning

confidence: 85%

“…Hepatocyte growth factor (HGF) stimulates cell proliferation and differentiation of various cell types 12 . For example, the differentiation of bone mesenchymal stem cells (BMSCs) can be induced through HGF-activated NF-кB signaling 13 . In mouse and human mammary glands, HGF acts as a morphogenic factor in mammary epithelial cells, generating tubular branching and well-constructed lumina during differentiation and development 14 .…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell

Jeong

Ham

Park

et al. 2017

Sci Rep

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MicroRNA-7 (miR-7) is a non-coding RNA of 23-nucleotides that has been shown to act as a tumor suppressor in various cancers including breast cancer. Although there have been copious studies on the action mechanisms of miR-7, little is known about how the miR is controlled in the mammary cell. In this study, we performed a genome-wide expression analysis in miR-7-transfected MCF-10A breast cell line to explore the upstream regulators of miR-7. Analysis of the dysregulated target gene pool predicted hepatocyte growth factor (HGF) as the most plausible upstream regulator of miR-7. MiR-7 was upregulated in MCF-10A cells by HGF, and subsequently downregulated upon treatment with siRNA against HGF. However, the expression of HGF did not significantly change through either an upregulation or downregulation of miR-7 expression, suggesting that HGF acts upstream of miR-7. In addition, the target genes of miR-7, such as EGFR, KLF4, FAK, PAK1 and SET8, which are all known oncogenes, were downregulated in HGF-treated MCF-10A; in contrast, knocking down HGF recovered their expression. These results indicate that miR-7 mediates the activity of HGF to suppress oncogenic proteins, which inhibits the development of normal cells, at least MCF-10A, into cancerous cells.

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Section: Discussionmentioning

confidence: 85%

Section: Introductionmentioning

confidence: 99%

MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell

Jeong

Ham

Park

et al. 2017

Sci Rep

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“…TEM examination demonstrated the undifferentiated characteristics of HYX1 cells, including large nucleus-to-cytoplasm ratio and underdeveloped organelles. ICG is a water soluble anionic complex that is uptaken by liver cells only and is used to evaluate hepatocyte function [26]. Hepatocytes are very important for glycogen storage and synthesis in vivo.…”

Section: Discussionmentioning

confidence: 99%

Human liver stem cells attenuate concanavalin A-induced acute liver injury by modulating myeloid-derived suppressor cells and CD4+ T cells in mice

Yang

et al. 2019

Stem Cell Res Ther

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BackgroundAcute liver failure (ALF) is a serious threat to the life of people all over the world. Finding an effective way to manage ALF is important. Human liver stem cells (HLSCs) are early undifferentiated cells that have been implicated in the regeneration and functional reconstruction of the liver. In this study, we aimed to evaluate the protective effects of the HLSC line HYX1 against concanavalin A (ConA)-induced acute liver injury.MethodsHYX1 cells were characterized by microscopy, functional assays, gene expression, and western blot analyses. We showed that HYX1 cells can differentiate into hepatocytes. We intraperitoneally injected HYX1 cells in mice and administered ConA via caudal vein injection 3, 6, 12, 24, and 48 h later. The effects of HYX1 cell transplantation were evaluated through blood tests, histology, and flow cytometry.ResultsHYX1 cells reduced the levels of alanine transaminase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) in serum and dramatically decreased the severity of liver injuries. Mechanistically, HYX1 cells promoted myeloid-derived suppressor cell (MDSC) migration into the spleen and liver, while reducing CD4+ T cell levels in both tissues. In addition, HYX1 cells suppressed the secretion of proinflammatory cytokines, such as tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ), but led to increased interleukin-10 (IL-10) production.ConclusionsThese results confirm the efficacy of HLSCs in the prevention of the ConA-induced acute liver injury through modulation of MDSCs and CD4+ T cell migration and cytokine secretion.Electronic supplementary materialThe online version of this article (10.1186/s13287-018-1128-2) contains supplementary material, which is available to authorized users.

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“…HGF has been demonstrated to be a potent antiapoptotic and mitogenic factor in repairing liver injury. Furthermore, HGF enhances the differentiation of MSCs toward HLCs via activation of NF-кB signaling in vitro [90]. To further improve the therapeutic effects of MSCs in APAP-induced liver injury, gene modification, which can specifically express growth factors, will contribute to MSC-based regenerative medicine in ALF models.…”

Section: Msc Transplantation For Apap-induced Liver Injurymentioning

confidence: 99%

Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury

Zhao

Wang

et al. 2020

Stem Cell Res Ther

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Acetaminophen (APAP)-induced injury is a common clinical phenomenon that not only occurs in a dosedependent manner but also occurs in some idiosyncratic individuals in a dose-independent manner. APAP overdose generally results in acute liver injury via the initiation of oxidative stress, endoplasmic reticulum (ER) stress, autophagy, liver inflammation, and microcirculatory dysfunction. Liver transplantation is the only effective strategy for treating APAP-induced liver failure, but liver transplantation is inhibited by scarce availability of donor liver grafts, acute graft rejection, lifelong immunosuppression, and unbearable costs. Currently, N-acetylcysteine (NAC) effectively restores liver functions early after APAP intake, but it does not protect against APAP-induced injury at the late stage. An increasing number of animal studies have demonstrated that mesenchymal stem cells (MSCs) significantly attenuate acute liver injury through their migratory capacity, hepatogenic differentiation, immunoregulatory capacity, and paracrine effects in acute liver failure (ALF). In this review, we comprehensively discuss the mechanisms of APAP overdose-induced liver injury and current therapies for treating APAP-induced liver injury. We then comprehensively summarize recent studies about transplantation of MSC and MSC derivatives for treating APAP-induced liver injury. We firmly believe that MSCs and their derivatives will effectively promote liver regeneration and liver injury repair in APAP overdose-treated animals and patients. To this end, MSC-based therapies may serve as an effective strategy for patients who are waiting for liver transplantation during the early and late stages of APAP-induced ALF in the near future.

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Hepatocyte growth factor‐induced differentiation of bone mesenchymal stem cells toward hepatocyte‐like cells occurs through nuclear factor‐kappa B signaling in vitro

Cited by 7 publications

References 24 publications

MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell

MicroRNA-7-5p mediates the signaling of hepatocyte growth factor to suppress oncogenes in the MCF-10A mammary epithelial cell

Human liver stem cells attenuate concanavalin A-induced acute liver injury by modulating myeloid-derived suppressor cells and CD4+ T cells in mice

Transplantation of mesenchymal stem cells and their derivatives effectively promotes liver regeneration to attenuate acetaminophen-induced liver injury

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