BMP‐7 functions as a novel hormone to facilitate liver regeneration

Sugimoto, Hikaru; Yang, Changqing; LeBleu, Valerie S.; Soubasakos, Mary A.; Giraldo, Mauricio; Zeisberg, Michael; Kalluri, Raghu

doi:10.1096/fj.06-6837com

Cited by 115 publications

(116 citation statements)

References 24 publications

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“…Although the liver does not normally produce BMP7, BMP7 receptors are found on hepatocytes, and neutralization of circulating BMP7 in a mouse partial hepatectomy model inhibited hepatocyte regeneration (54). In the reverse experiment, these authors demonstrated increased liver proliferation after partial hepatectomy when recombinant BMP7 was infused into the mice.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4α in Adult Mice

Bonzo

Ferry

Matsubara

et al. 2012

Journal of Biological Chemistry

187

228

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Background: HNF4␣ is a key factor regulating hepatocyte differentiation and liver-specific functions. Results: Acute disruption of HNF4␣ in the adult liver causes rapid hepatocyte proliferation through direct and indirect control of multiple pathways. Conclusion: HNF4␣ is necessary to maintain the differentiated state of hepatocytes in adult liver. Significance: HNF4␣ expression maintains normal liver function, and its loss stimulates hepatocytes proliferation, possibly leading to cancer.

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Section: Discussionmentioning

confidence: 99%

Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4α in Adult Mice

Bonzo

Ferry

Matsubara

et al. 2012

Journal of Biological Chemistry

187

228

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“…Accumulated evidence suggested that BMP-7 signaling was beneficial to resolve established organ damage, especially renal and hepatic progressive fibrosis (Wang et al 2006;Sugimoto et al 2007;Zeisberg and Kalluri 2008). Of note, small peptide agonists of BMP-7 receptors have been developed to inhibit kidney inflammation, tissue damage, and fibrosis (Sugimoto et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…Of note, small peptide agonists of BMP-7 receptors have been developed to inhibit kidney inflammation, tissue damage, and fibrosis (Sugimoto et al 2007). However, to date, no small regulator targeting the myocardial fibrosis was reported.…”

Section: Discussionmentioning

confidence: 99%

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Xiao

et al. 2018

Tohoku J. Exp. Med.

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Myocardial fibrosis after acute myocardial infarction (AMI) is one of the main causes of myocardial remodeling and heart function abnormalities. Bone morphogenetic protein-7 (BMP-7) has been reported to play essential roles in anti-fibrosis. In this study, we demonstrated the role of exogenous BMP-7 on myocardial fibrosis and heart function recovery after AMI. A rat model of AMI was established via ligation of the left anterior descending coronary artery (LAD). Twenty rats were grouped into sham group which underwent chest open operation, but did not receive LAD ligation. Another 40 rats underwent LAD ligation were randomly grouped into saline-treated group (n = 20) and BMP-7-treated group (n = 20) which received saline treatment or exogenous BMP-7 treatment for 14 days, respectively. Two weeks after LAD ligation, the survival rate of BMP-7-treated AMI group was significantly improved compared to the saline group. Moreover, the cardiac function was preserved as shown by echocardiography examination, and the infarcted size was limited upon BMP-7 treatment. In addition, we investigated the role of TGF-β1 signaling pathway in BMP-7-mediated cardioprotective effects by analyzing the expression levels of TGF-β1, Smad 2 and Smad 3 in the infarct zone, border zone, and non-infarct zone. Western blot and quantitative PCR results suggested that BMP-7 attenuated myocardial fibrosis through counteracting TGF-β1 signaling pathway, thereby exerting cardioprotective effects. In conclusion, our data provide a potential therapeutic direction for preserving cardiac function and improving prognosis of AMI patients.

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“…Numerous growth factors and cytokines have been implicated in the initiation and control of this regenerative response [1,[10][11][12][13][14][15][16], with the activation of seemingly critical transcription factors, such as AP-1, NFκB and STAT-3. Liver injury can be associated with a defective intestinal barrier, leading to exposure to bacterial products such as lipopolysaccharides and components of the innate immune system (complement fragments), and their activation of the NFκB pathway in Kupffer cells, leading to the production and secretion Figure 1.…”

Section: Hepatocytesmentioning

confidence: 99%

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

Alison

Islam

Lim

2008

The Journal of Pathology

201

149

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The worldwide shortage of donor livers to transplant end stage liver disease patients has prompted the search for alternative cell therapies for intractable liver diseases, such as acute liver failure, cirrhosis and hepatocellular carcinoma (HCC). Under normal circumstances the liver undergoes a low rate of hepatocyte 'wear and tear' renewal, but can mount a brisk regenerative response to the acute loss of two-thirds or more of the parenchymal mass. A body of evidence favours placement of a stem cell niche in the periportal regions, although the identity of such stem cells in rodents and man is far from clear. In animal models of liver disease, adopting strategies to provide a selective advantage for transplanted hepatocytes has proved highly effective in repopulating recipient livers, but the poor success of today's hepatocyte transplants can be attributed to the lack of a clinically applicable procedure to force a similar repopulation of the human liver. The activation of bipotential hepatic progenitor cells (HPCs) is clearly vital for survival in many cases of acute liver failure, and the signals that promote such reactions are being elucidated. Bone marrow cells (BMCs) make, at best, a trivial contribution to hepatocyte replacement after damage, but other BMCs contribute to the hepatic collagen-producing cell population, resulting in fibrotic disease; paradoxically, BMC transplantation may help alleviate established fibrotic disease. HCC may have its origins in either hepatocytes or HPCs, and HCCs, like other solid tumours appear to be sustained by a minority population of cancer stem cells.

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BMP‐7 functions as a novel hormone to facilitate liver regeneration

Cited by 115 publications

References 24 publications

Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4α in Adult Mice

Suppression of Hepatocyte Proliferation by Hepatocyte Nuclear Factor 4α in Adult Mice

Exogenous BMP-7 Facilitates the Recovery of Cardiac Function after Acute Myocardial Infarction through Counteracting TGF-<i>β</i>1 Signaling Pathway

Stem cells in liver regeneration, fibrosis and cancer: the good, the bad and the ugly

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