BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration

Herrera, Blanca; Addante, Annalisa; Sánchez, Aránzazu

doi:10.3390/ijms19010039

Cited by 54 publications

(50 citation statements)

References 180 publications

(224 reference statements)

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“…The role of BMP9 in liver homeostasis is still unclear and controversial [10,11]. BMP9 was reported to be an autocrine/paracrine cytokine inhibiting adult (non-malignant) hepatocyte proliferation [3].…”

Section: Introductionmentioning

confidence: 99%

Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Desroches-Castan

Tillet

Ricard

et al. 2019

Cells

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The aim of the present work was to address the role of BMP9 in different genetic backgrounds (C57BL/6, BALB/c, and 129/Ola) of mice deleted for Bmp9. We found that Bmp9 deletion led to premature mortality only in the 129/Ola strain. We have previously shown that Bmp9 deletion led to liver sinusoidal endothelial cells (LSEC) capillarization and liver fibrosis in the 129/Ola background. Here, we showed that this is not the case in the C57BL/6 background. Analysis of LSEC from Wild-type (WT) versus Bmp9-KO mice in the C57BL/6 background showed no difference in LSEC fenestration and in the expression of differentiation markers. Comparison of the mRNA expression of LSEC differentiation markers between WT C57BL/6 and 129/Ola mice showed a significant decrease in Stabilin2, Plvap, and CD209b, suggesting a more capillary-like phenotype in WT C57BL/6 LSECs. C57BL/6 mice also had lower BMP9 circulating concentrations and hepatic Vegfr2 mRNA levels, compared to the 129/Ola mice. Taken together, our observations support a role for BMP9 in liver endothelial cell fenestration and prevention of fibrosis that is dependent on genetic background. It also suggests that 129/Ola mice are a more suitable model than C57BL/6 for the study of liver fibrosis subsequent to LSEC capillarization.

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Section: Introductionmentioning

confidence: 99%

Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Desroches-Castan

Tillet

Ricard

et al. 2019

Cells

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“…While the pivotal role of transforming growth factor beta (TGF-β) as a master cytokine controlling the progression of chronic liver disease is well established, 5 the implication of other TGF-β superfamily members such as the bone morphogenetic proteins (BMP) remains to be fully elucidated. 6 Of particular interest is BMP9, a member of this family that is primarily expressed in liver, and present in serum at bioactive concentration. 7,8 Our laboratory and others have shown that BMP9 promotes proliferation, survival and invasion in hepatocellular carcinoma cells, supporting a protumorigenic role of BMP9 in liver.…”

Section: Introductionmentioning

confidence: 99%

Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC‐induced cholestatic liver injury

Addante

Roncero

Almalé

et al. 2018

Liver International

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“…Induction of stem-cell pluripotent genes is indicative of cellular reprogramming to a dedifferentiated state that occurs during HCC development [27]. BMP signaling has a complex role in regulating iron homeostasis, liver fibrosis, and liver regeneration [28]. TGF-β is known to induce transdifferentiation and production of collagen and extracellular matrix proteins in hepatic stellate cells, and deletion of the TGF-β receptor in hepatocytes has been shown to alleviate NASH [29].…”

Section: Discussionmentioning

confidence: 99%

A Low Iron Diet Protects from Steatohepatitis in a Mouse Model

et al. 2019

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High tissue iron levels are a risk factor for multiple chronic diseases including type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). To investigate causal relationships and underlying mechanisms, we used an established NAFLD model—mice fed a high fat diet with supplemental fructose in the water (“fast food”, FF). Iron did not affect excess hepatic triglyceride accumulation in the mice on FF, and FF did not affect iron accumulation compared to normal chow. Mice on low iron are protected from worsening of markers for non-alcoholic steatohepatitis (NASH), including serum transaminases and fibrotic gene transcript levels. These occurred prior to the onset of significant insulin resistance or changes in adipokines. Transcriptome sequencing revealed the major effects of iron to be on signaling by the transforming growth factor beta (TGF-β) pathway, a known mechanistic factor in NASH. High iron increased fibrotic gene expression in vitro, demonstrating that the effect of dietary iron on NASH is direct. Conclusion: A lower tissue iron level prevents accelerated progression of NAFLD to NASH, suggesting a possible therapeutic strategy in humans with the disease.

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BMP Signalling at the Crossroad of Liver Fibrosis and Regeneration

Cited by 54 publications

References 180 publications

Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Differential Consequences of Bmp9 Deletion on Sinusoidal Endothelial Cell Differentiation and Liver Fibrosis in 129/Ola and C57BL/6 Mice

Bone morphogenetic protein 9 as a key regulator of liver progenitor cells in DDC‐induced cholestatic liver injury

A Low Iron Diet Protects from Steatohepatitis in a Mouse Model

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