Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

Chu, Chun-Ping; Zhang, Da-Jin; Shi, Bingxing; Du, Shao Jun; Wu, Danli; Wei, Ping; Zhong, Gen-Shen; Guo, Zi-Kuan; Liu, Yang; Wang, Lisheng; Wu, Cheng-Feng

doi:10.1002/hep.22126

Cited by 15 publications

(34 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Primary hepatocytes were isolated from male Wistar rats weighing around 200 g as described in our previous work [1]. Cells were cultured in Dulbecco's modified Eagle's medium (Invitrogen, Carlsbad, CA, USA) supplemented with 10% heat-inactivated fetal bovine serum(FBS) (Sigma, St. Louis, MO, USA), 1% nonessential amino acid (Sigma), 1% sodium pyruvate (Sigma), and 1% penicillin/ streptomycin solution (Sigma) at 37.0°C under a humidified atmosphere of 5% CO2.…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Cell proliferation and apoptosis assay Cell proliferation was determined using the MTT and 3 H-TdR DNA incorporation assay as described previously [1,4]. Apoptotic cells were detected using FITC-conjugated Annexin V (Caltag Laboratories, Burlingame, CA, USA) and propidium iodide (PI).…”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Levels of HPPCn mRNA were detected with real-time PCR and HPPCn protein levels were analyzed using western blot as described in [1].…”

Section: Hppcn Expressionmentioning

confidence: 99%

“…The HPPCn mRNA level increases in partially hepatectomized mice following liver injury. Recombinant human HPPCn protein (rhHPPCn) was shown to stimulate hepatocyte proliferation in vitro and in vivo, by activating signaling pathways including sphingosine kinase-1, extracellular signal regulated kinase, and activator of transcription 3 [1]. Furthermore, our previous investigations have demonstrated that rhHPPCn, as a hepatocyte proliferation stimulator, could protect hepatocytes from carbon tetrachloride-induced injury [2,3].…”

Section: Introductionmentioning

confidence: 97%

“…Hepatopoietin Cn (HPPCn) is a novel member of the leucine-rich acidic nuclear protein family (LANP) that was first purified from a crude extract of calf liver by our group [1]. The HPPCn mRNA level increases in partially hepatectomized mice following liver injury.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Involvement of Hepatopoietin Cn in the development of human hepatocellular carcinoma

Zhu

Li²,

Liu³

et al. 2010

Clin Exp Metastasis

Self Cite

View full text Add to dashboard Cite

Hepatopoietin Cn (HPPCn) is a novel nuclear protein with the ability to promote liver regeneration. In the present study, we investigated the expression profile of HPPCn and its functional activity in human hepatocellular carcinoma (HCC) cell line and tissue samples. HPPCn expression was detected in HCC cell lines and 54 paired HCC carcinomas by immunochemical staining and Western blotting. The functional activity of HPPCn in cell lines was evaluated by MTT and colony formation assays and with nude mouse model. The correlation of HPPCn expression with clinicopathological characteristics of 54 HCC patients was also analyzed. Our results showed that HPPCn protein was prominently located within the nuclei of hepatocytes and the expression level was evidently increased in HepG2 and Bel7402 cell lines compared with L02 normal hepatocytes. HPPCn silencing by small interfering RNA greatly suppressed HepG2 cell proliferation and colony formation capacity and the inhibitory effect was also observed in a Balb/c-null mouse model. The silencing HPPCn expression effectively enhanced the apoptosis of HepG2 cells. In addition, HPPCn expression was detected in 48 of 54 (89%) human HCC tissues in sharp contrast with the corresponding non-tumor liver tissues. HPPCn protein was mainly accumulated in the tumor nucleus. The elevated expression of HPPCn protein in tumors was significantly associated with poor tumor cellular differentiation and present of vascular invasion. Patients with higher HPPCn expression in tumors had significantly shorter overall survival (OS) of both all of patients and the patients at the early stage. On multivariate Cox analysis, elevated expression of HPPCn in tumors was found to be an independent prognostic factor for OS. Therefore, these data suggest that HPPCn expression might be involved in the development of HCC and could be served as a promising biomarker.

show abstract

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Levels of HPPCn mRNA were detected with real-time PCR and HPPCn protein levels were analyzed using western blot as described in [1].…”

Section: Hppcn Expressionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Involvement of Hepatopoietin Cn in the development of human hepatocellular carcinoma

Zhu

Li²,

Liu³

et al. 2010

Clin Exp Metastasis

Self Cite

View full text Add to dashboard Cite

show abstract

Cracking the ANP32 whips: Important functions, unequal requirement, and hints at disease implications

Reilly

Hamiche

et al. 2014

BioEssays

View full text Add to dashboard Cite

The acidic (leucine-rich) nuclear phosphoprotein 32 kDa (ANP32) family is composed of small, evolutionarily conserved proteins characterized by an N-terminal leucine-rich repeat domain and a C-terminal low-complexity acidic region. The mammalian family members (ANP32A, ANP32B, and ANP32E) are ascribed physiologically diverse functions including chromatin modification and remodelling, apoptotic caspase modulation, protein phosphatase inhibition, as well as regulation of intracellular transport. In addition to reviewing the widespread literature on the topic, we present a concept of the ANP32s as having a whip-like structure. We also present hypotheses that ANP32C and other intronless sequences should not currently be considered bona fide family members, that their disparate necessity in development may be due to compensatory mechanisms, that their contrasting roles in cancer are likely context-dependent, along with an underlying hypothesis that ANP32s represent an important node of physiological regulation by virtue of their diverse biochemical activities.

show abstract

Hepatopoietin Cn reduces ethanol‐induced hepatoxicity via sphingosine kinase 1 and sphingosine 1‐phosphate receptors

Liu¹,

Saiyan²,

Men

et al. 2013

The Journal of Pathology

Self Cite

View full text Add to dashboard Cite

The hepatic growth factor hepatopoietin Cn (HPPCn) prevents liver injury induced by carbon tetrachloride in rats. Sphingosine 1-phosphate (S1P) is a bioactive sphingolipid produced by sphingosine kinase (SphK). S1P and S1P receptors (S1PRs) are involved in liver fibrogenesis and oxidative injury. This work sought to understand the mechanism by which SphK/S1P/S1PRs are involved in the protective effects of HPPCn on ethanol-induced liver injury and fibrosis. Transgenic mice with liver-specific overexpression of HPPCn (HPPCn(liver) (+/+)) were generated. Two ethanol feeding protocols were used to assess the protective effect of HPPCn on acute and chronic liver injury in mice. Specific inhibitors of S1PR1, S1PR2 and S1PR3 and siRNA were used to examine the roles of S1PRs in hepatic stellate cell (HSC) activation and hepatocyte apoptosis. Increased HPPCn expression in transgenic mice attenuated fibrosis induced by ethanol and carbon tetrachloride (CCl4). Treatment with recombinant human HPPCn prevented human hepatocyte apoptosis and HSC activation. JTE-013 or S1PR2-siRNA attenuated the effect of HPPCn on HSC activation induced by tumour necrosis factor-α (TNF-α). Consistent with the effect of N,N-dimethylsphingosine (DMS), suramin or S1PR3-siRNA treatment blocked HPPCn-induced Erk1/2 phosphorylation in human hepatocytes. This study demonstrated that HPPCn attenuated oxidative injury and fibrosis induced by ethanol feeding and that the SphK1/S1P/S1PRs signalling pathway contributes to the protective effect of HPPCn on hepatocyte apoptosis and HSC activation.

show abstract

Isolation and functional identification of a novel human hepatic growth factor: Hepatopoietin Cn

Cited by 15 publications

References 35 publications

Involvement of Hepatopoietin Cn in the development of human hepatocellular carcinoma

Involvement of Hepatopoietin Cn in the development of human hepatocellular carcinoma

Cracking the ANP32 whips: Important functions, unequal requirement, and hints at disease implications

Hepatopoietin Cn reduces ethanol‐induced hepatoxicity via sphingosine kinase 1 and sphingosine 1‐phosphate receptors

Contact Info

Product

Resources

About