Nogo‐<scp>B</scp>: A potential indicator for hepatic cirrhosis and regulator in hepatic stellate cell activation

Men, Ruoting; Wen, Maoyao; Dan, Xuelian; Zhu, Yongjun; Wang, Wanqin; Li, Junli; Wu, Wenchao; Liu, Xiaojing; Yang, Li

doi:10.1111/hepr.12324

Cited by 26 publications

(29 citation statements)

References 29 publications

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“…However, few new markers associated with prognosis or malignant behavior of ICC has been determined (Oishi et al 2012;Shimada et al 2010). In this study we studied Nogo-B, which has recently been identified as a potential marker of hepatic fibrosis (Zhang et al 2011;Gao et al 2013;Tashiro et al 2013;Men et al 2015) and as a potential enhancer of bile duct proliferation (Zhang Each survival rate is shown as % value, based on our analytical software.…”

Section: Macroscopic Findingmentioning

confidence: 99%

“…In the liver, Nogo-B is expressed specifically in cholangiocytes and non-parenchymal cells, but not in hepatocytes (Zhang et al 2011). Studies in cirrhotic patients and experimental models of fibrosis/cirrhosis suggest that Nogo-B is downregulated in liver fibrotic/cirrhosis or apoptosis of hepatic stellate cells Men et al 2015). Further, deletion of Nogo-B results in amelioration of liver cirrhosis and portal hypertension in mice with biliary cirrhosis Men et al 2015).…”

Section: Introductionmentioning

confidence: 99%

“…Studies in cirrhotic patients and experimental models of fibrosis/cirrhosis suggest that Nogo-B is downregulated in liver fibrotic/cirrhosis or apoptosis of hepatic stellate cells Men et al 2015). Further, deletion of Nogo-B results in amelioration of liver cirrhosis and portal hypertension in mice with biliary cirrhosis Men et al 2015). From the above previous reports, given that Nogo-B is expressed in cholangio-cytes and that deletion of Nogo-B results in attenuation of biliary cirrhosis in which cholangiocyte proliferation plays a central role (Zhang et al 2011), we hypothesized that decreased Nogo-B expression might stimulate cancer cell proliferation, tumor growth or invasion, and may play a significant role in poor prognosis of patients with ICC.…”

Section: Introductionmentioning

confidence: 99%

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Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Nanashima

Hatachi

Tominaga

et al. 2016

Tohoku J. Exp. Med.

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Nogo-B, located in the endoplasmic reticulum, is an isoform belonging to the reticulon protein family, which is expressed specifically in cholangiocytes and non-parenchymal cells in the liver. Nogo-B expression is down-regulated with the progression of liver fibrosis, but its distinct function in liver malignancies has not been fully clarified. We have hypothesized that Nogo-B expression may be altered in intrahepatic cholangiocarcinoma (ICC), a relatively rare type of primary liver cancer with highly malignant behavior. The present study aimed to investigate the relationship between Nogo-B expression, assessed by immunohistochemical staining, and clinicopathological factors and prognosis in 34 ICC patients. Positive expression was observed in 19 (56%) of 34 ICC specimens: 6 patients (18%) with positivity levels of 1+ (positive cells in 10-50% of cancer cells) and 13 patients (38%) with 2+ (positive cells over 50%). Importantly, the remaining 15 patients (44%) were categorized as negative expression (Nogo-B-positive cells, less than 10%). Conversely, the mass-forming type of ICC tended to express Nogo-B with the degree of 2+ positivity, compared to the periductal infiltration type (p = 0.064), and the mass-forming type showed a better 5-year survival rate (66% vs. 5%) after hepatectomy (p < 0.05). However, the degree of positivity was not associated with tumor relapse rate, disease-free and overall survival, although each of the periductal infiltration type, intrahepatic metastasis, larger tumor size, and lower microvessel counts was associated with lower survival rates. We propose that Nogo-B expression is down-regulated in ICC, the implication of which, however, remains to be investigated.

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Section: Macroscopic Findingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Nanashima

Hatachi

Tominaga

et al. 2016

Tohoku J. Exp. Med.

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show abstract

“…Although remarkable progress has been achieved in understanding the molecular mechanism and developing comprehensive therapies for HCC, rendering incurable HCC curable in certain patients, the prognosis of patients with HCC remains largely disappointing [14]. Nogo-B was reported to be preferentially expressed in non-parenchymal cells in the liver, and upregulation of Nogo-B expression has been detected in patients' cirrhotic liver tissues [15]. Nogo-B is potentially involved in the activation of hepatic stellate cells (HSCs), as knockdown of Nogo-B in HSCs dramatically impaired HSC activation [15].…”

Section: Introductionmentioning

confidence: 99%

“…Nogo-B was reported to be preferentially expressed in non-parenchymal cells in the liver, and upregulation of Nogo-B expression has been detected in patients' cirrhotic liver tissues [15]. Nogo-B is potentially involved in the activation of hepatic stellate cells (HSCs), as knockdown of Nogo-B in HSCs dramatically impaired HSC activation [15]. Nonetheless, the role of vascular endothelial Nogo-B in HCC progression remains unclear.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

Li¹,

Cheng²,

Huang³

et al. 2018

Oncotarget

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An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization

et al. 2017

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Background Nogo-B (Reticulon 4B) is an endoplasmic reticulum (ER) resident protein that regulates ER structure and function. Since ER stress is known to induce M2 macrophage polarization, we examined whether Nogo-B regulates M1/M2 polarization of Kupffer cells and alters the pathogenesis of alcoholic liver disease (ALD). Methods M1 and M2 phenotypes were assessed in relation to Nogo-B expression and disease severity in liver specimens from ALD patients (NCT01875211). Liver specimens from wild-type (WT) and Nogo-B knockout (KO) mice fed control or Lieber-DeCarli ethanol liquid diet (5% ethanol) for 6 weeks were analyzed for liver injury and steatosis. Kupffer cells isolated from WT and Nogo-B KO mice were assessed for M1 and M2 activation. Results A significant positive correlation was observed between Nogo-B positive Kupffer cells and disease severity in ALD patients (n=30, r=0.66, p=0.048). Further, Nogo-B positive Kupffer cells correlated with M1 activation (iNOS) (r=0.50, p=0.05) and negatively with markers of M2 status (CD163) (r=−0.48, p=0.07) in these patients. WT mice exhibited significantly increased liver injury (p<0.05) and higher hepatic triglyceride levels (p<0.01), compared to Nogo-B KO mice in response to chronic ethanol feeding. Nogo-B in Kupffer cells promoted M1 polarization, whereas absence of Nogo-B increased ER stress and M2 polarization in Kupffer cells. Conclusion Nogo-B is permissive for M1 polarization of Kupffer cells, thereby accentuating liver injury in ALD in humans and mice. Nogo-B in Kupffer cells may represent a new therapeutic target for ALD.

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Nogo‐B: A potential indicator for hepatic cirrhosis and regulator in hepatic stellate cell activation

Abstract: Circulating Nogo-B may be an effective indicator for liver cirrhosis. Nogo-B inhibition could diminish HSC activation, in which alleviating ER stress may be one of the mechanisms, suggesting a potential approach to interference Nogo-B in liver fibrosis.

Cited by 26 publications

References 29 publications

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

Down-Regulation of Nogo-B Expression as a Newly Identified Feature of Intrahepatic Cholangiocarcinoma

WITHDRAWN: Endothelial Nogo-B suppresses cancer cell proliferation via a paracrine TGF-β/Smad signaling

An endoplasmic reticulum protein, Nogo‐B, facilitates alcoholic liver disease through regulation of kupffer cell polarization

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