Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis

Li, Changyong; Kong, Yaxian; Wang, Hong; Wang, Shuling; Yu, Heng; Liu, Xin; Yang, Lin; Xie, Juanying; Li, Lingsong; Li, Liying

doi:10.1016/j.jhep.2009.01.028

Cited by 168 publications

(164 citation statements)

References 50 publications

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“…225 In addition, platelet-derived growth factor was shown to exert an effect as MSC chemoattractant. 127,201,202 As expected, di Bonzo et al 50 and Li et al 226 have recently shown that many MSCs recruited to the fibrotic liver become indeed myofibroblasts.…”

Section: Msc Contribution To Liver Fibrogenic Processsupporting

confidence: 55%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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Mesenchymal stem (stromal) cells (MSCs) are a source of circulating progenitors that are able to generate cells of all mesenchymal lineages and to cover cellular demands of injured tissues. The extent of their transdifferentiation plasticity remains controversial. Cells with MSC properties have been obtained from diverse tissues after purification and expansion in vitro. These cellular populations are heterogeneous and under certain conditions show pluripotent-like properties. MSCs present immunosuppressive and anti-inflammatory features and high migratory capacity toward inflamed or remodeling tissues. In this study we review available data regarding factors and signaling axes involved in the chemoattraction and engraftment of MSCs to an injured tissue or to a tissue undergoing active remodeling. Moreover, experimental evidence in support of uses of MSCs as vehicles of therapeutic genes is discussed. Because of its regenerative capacity and its particular immune properties, the liver is a good model to analyze the potential of MSCbased therapies. Finally, the potential application of MSCs and genetically modified MSCs in liver fibrosis and hepatocellular carcinoma (HCC) is proposed in view of available evidence.

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Section: Msc Contribution To Liver Fibrogenic Processsupporting

confidence: 55%

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

et al. 2010

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“…Recent studies suggested that TGF-b increases SphK1 and S1P production in many tissues, and subsequently stimulates tissue fibrosis in tissues including the human lung, liver, and heart. [8][9][10] In light of these findings, and the TGF-b-stimulated SphK1/S1P production in renal TECs seen in Figure 3, we hypothesized that the SphK1/S1P pathway is linked to upregulation of miR-21 by TGF-b, and we sought to investigate the interaction between TGF-b/SphK1/S1P and miR-21 in renal TECs. As shown in Figure 3, when the TGF-b-stimulated increase in SphK1 expression was inhibited with siRNA, TGF-b-stimulated upregulation of miR-21 was abolished.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] To investigate whether SphK and S1P are regulated by TGF-b during renal fibrosis in TECs, we first evaluated the S1P level using an ELISA assay with TECs treated with 1, 2, 3, 5, and 10 ng/mL TGF-b. Figure 3(a) shows that TGF-b induced S1P production in a dose-dependent manner, with an approximate twofold increase at 10 ng/mL TGF-b.…”

Section: Inhibition Of Mir-21 Decreases Tgf-b-induced Ecm Protein Expmentioning

confidence: 99%

“…TGF-b increases SphK1 and S1P synthesis in human lung fibroblasts, and inhibition of SphK1 reduces S1P production and TGF-b-mediated signal transduction. 8,9 Additionally, TGF-b increases collagen production in cardiac fibroblasts by activating SphK and S1P signaling. 10 MicroRNAs (miRNAs) are short (21-23 nucleotides), endogenous, non-coding, single-stranded RNAs that constitute a large class of important endogenous regulators of gene expression and cellular activity.…”

Section: Introductionmentioning

confidence: 99%

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Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells

Liu

Hong

Wang

et al. 2015

Exp Biol Med (Maywood)

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Renal fibrosis is a progressive pathological change characterized by tubular cell apoptosis, tubulointerstitial fibroblast proliferation, and excessive deposition of extracellular matrix (ECM). miR-21 has been implicated in transforming growth factor-b (TGF-b)-stimulated tissue fibrosis. Recent studies showed that sphingosine kinase/sphingosine-1-phosphate (SphK/S1P) are also critical for TGF-b-stimulated tissue fibrosis; however, it is not clear whether SphK/S1P interacts with miR-21 or not. In this study, we hypothesized that SphK/S1P signaling is linked to upregulation of miR-21 by TGF-b. To verify this hypothesis, we first determined that miR-21 was highly expressed in renal tubular epithelial cells (TECs) stimulated with TGF-b by using qRT-PCR and Northern blotting. Simultaneously, inhibition of miR-21, mediated by the corresponding antimir, markedly decreased the expression and deposition of type I collagen, fibronectin (Fn), cysteine-rich protein 61 (CCN1), a-smooth muscle actin, and fibroblastspecific protein1 in TGF-b-treated TECs. ELISA and qRT-PCR were used to measure the S1P and SphK1 levels in TECs. S1P production was induced by TGF-b through activation of SphK1. Furthermore, it was observed that TGF-b-stimulated upregulation of miR-21 was abolished by SphK1 siRNA and was restored by the addition of exogenous S1P. Blocking S1PR 2 also inhibited upregulation of miR-21. Additionally, miR-21 overexpression attenuated the repression of TGF-b-stimulated ECM deposition and epithelial-mesenchymal transition by SphK1 and S1PR 2 siRNA. In summary, our study demonstrates a link between SphK1/S1P and TGF-b-induced miR-21 in renal TECs and may represent a novel therapeutic target in renal fibrosis.

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“…This molecule has been implicated in the recruitment of cultured MSCs after chemically-induced liver injury. Li et al showed that recruited MSCs supplied a new source of myofibroblasts and thus supported the process of fibrosis (Li et al, 2009). Further signalling studies by Kong and colleagues identified that S1P-mediated migration of MSCs occurred via S1P receptor 1 and 3, initiating G i -dependent activation of ERK1/2 signalling .…”

Section: Mechanisms Of Msc and Pericyte Recruitment To Sites Of Injurymentioning

confidence: 98%

Pericytes, mesenchymal stem cells and their contributions to tissue repair

Wong

Rowley

Redpath

et al. 2015

Pharmacology & Therapeutics

148

110

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Regenerative medicine using mesenchymal stem cells for the purposes of tissue repair has garnered considerable public attention due to the potential of returning tissues and organs to a normal, healthy state after injury or damage has occurred. To achieve this, progenitor cells such as pericytes and bone marrow-derived mesenchymal stem cells can be delivered exogenously, mobilised and recruited from within the body or transplanted in the form organs and tissues grown in the laboratory from stem cells. In this review, we summarise the recent evidence supporting the use of endogenously mobilised stem cell populations to enhance tissue repair along with the use of mesenchymal stem cells and pericytes in the development of engineered tissues. Finally, we conclude with an overview of currently available therapeutic options to manipulate endogenous stem cells to promote tissue repair.

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Homing of bone marrow mesenchymal stem cells mediated by sphingosine 1-phosphate contributes to liver fibrosis

Cited by 168 publications

References 50 publications

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Mesenchymal stem cells as therapeutic tools and gene carriers in liver fibrosis and hepatocellular carcinoma

Transforming growth factor-β-sphingosine kinase 1/S1P signaling upregulates microRNA-21 to promote fibrosis in renal tubular epithelial cells

Pericytes, mesenchymal stem cells and their contributions to tissue repair

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