Research progress of neuregulin 4 biological function / 生理学报

Neuregulin 4 (NRG4) is a kind of protein containing epidermal growth factor (EGF)-like domains, mainly expressed and secreted by brown adipocytes. It specifically activates EGF receptor ErbB4 (v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 4) to stimulate cell proliferation, inhibit apoptosis and improve energy metabolism of cells. Increasing evidence has shown that NRG4 plays an important role in epithelial cell-related diseases, cardiovascular diseases, tumors and glycolipid metabolic diseases, and therefore it could be a potential therapeutic target of some diseases.

Upregulation of epidermal growth factor receptor 4 in oral leukoplakia / 国际口腔科学杂志·英文版

In the present study, we investigate the expression profile of the epidermal growth factor receptor family, which comprises EGFR/ErbB1, HER2/ErbB2, HER3/ErbB3 and HER4/ErbB4 in oral leukoplakia (LP). The expression of four epidermal growth factor receptor (EGFR) family genes and their ligands were measured in LP tissues from 14 patients and compared with levels in 10 patients with oral lichen planus (OLP) and normal oral mucosa (NOM) from 14 healthy donors by real-time polymerase chain reaction (PCR) and immunohistochemistry. Synchronous mRNA coexpression of ErbB1, ErbB2, ErbB3 and ErbB4 was detected in LP lesions. Out of the receptors, only ErbB4 mRNA and protein was more highly expressed in LP compared with NOM tissues. These were strongly expressed by epithelial keratinocytes in LP lesions, as shown by immunohistochemistry. Regarding the ligands, the mRNA of Neuregulin2 and 4 were more highly expressed in OLP compared with NOM tissues. Therefore, enhanced ErbB4 on the keratinocytes and synchronous modulation of EGFR family genes may contribute to the pathogenesis and carcinogenesis of LP.

Neuregulins Action and Signaling Pathway in the Nervous System / 대한해부학회지

The neuregulins (NRGs) are a family of proteins containing an epidermal growth factor (EGF)-like motif that mediates important functions not only in the nervous system but also in the heart, breast and other organ systems. NRG1 was first found to function in the nervous system in the proliferation of Schwann cells, and in the regulation of nicotinic acetylcholine receptor (AChR) transcription at the neuromuscular junction (NMJ). NRGs have multiple biological functions. In the brain, NRG signaling regulates early fate determination, differentiation, migration, synaptic activity of target cell and the expression of other neurotransmitter receptors and survival of satellite cells, Schwann cells and oligodendrocytes. There is also evidence for involvement of NRGs signaling in the pathogenesis of disease, including breast cancer, multiple sclerosis, traumatic brain injury and Hirschsprung's disease. Especially, both NRG1 and ErbB4 have emerged as susceptibility genes of schizophrenia. In this review, I will summarize the latest findings regarding the spectrum of NRG-ErbB action and signaling pathways in the developing and adult nervous system.

Effects of recombined neuregulin on healthy Macaca mulatta hearts / 生物医学工程学杂志

To explore the effects of recombined Neuregulin on the heart of healthy Macaca mulatta, 10 healthy adult Macaca mulatta were randomly divided into two groups and were injected with the same doses of recombined Neuregulin and normal saline, respectively. At the same time, related indices were detected by 2-dimensional echocardiography and M-mode echocardiography. All indices were compared between the two groups and among different phases. Recombined Neuregulin had effects on LVEDD (left ventricular end-diastolic diameter), LVEDV (left ventricular end-diastolic volume), LVESV (left ventricular end-systolic volume) and SV (Stroke volume), and the effects changed with time. However, no significant changes were seen on EF (Ejection fraction) and FS (Fractional shortening). In conclusion, recombined Neuregulin has effects on the left ventricular volume of healthy Macaca mulatta, but no significant effect on cardiac contractility.

Effects of neuregulin on cardiac myocyte apoptosis and PI-3K signal transduction pathway in rapid pacing-induced heart failure in rhesus monkeys / 中南大学学报(医学版)

OBJECTIVE@#To explore the protective effect of neuregulin against cardiac myocyte injury in pacing-induced heart failure in rhesus monkeys and its mechanism.@*METHODS@#Rapid pacing was used to induce heart failure in rhesus monkeys. Aorta intubation was used to perform hemodynamic measurements such as the peak positive rate of of left ventricular pressure (LVdP/dtmax) and left ventricular systolic, end-diastolic blood pressures (LVSP and LVEDP, respectively) 17 days after the pacing. N-terminal pro-brain natriuretic peptide (BNP), as molecular marker of heart failure, was also measured by electrochemical luminescence immunoassay. The apoptosis of cardiac myocyte was observed by Tunel method. Western blot was used to detect the PKB activity and the relative amounts of Bcl-xl protein in the left ventricular free walls.@*RESULTS@#After the daily intravenous injection of 3microg/kg recombinated neuregulin for 10 days, LVdP/dtmax increased significantly while BNP decreased remarkably. The apoptotic index was obviously lower, and Bcl-xl and activity of PKB were higher.@*CONCLUSION@#Neuregulin protects against rapid pacing-induced apoptosis in heart failure in rhesus monkeys and the mechanism might be attributed to the increase of the activity of PKB and Bcl-xl protein.

Porcine vesical acellular matrix graft of tunica albuginea for penile reconstruction / 亚洲男科学杂志(英文版)

<p><b>AIM</b>To characterize the feasibility of the surgical replacement of the penile tunica albuginea (TA) and to evaluate the value of a porcine bladder acellular matrix (BAM) graft.</p><p><b>METHODS</b>Acellular matrices were constructed from pigs' bladders by cell lysis, and then examined by scanning electron microscopy (SEM). Expression levels of the mRNA of the vascular endothelial growth factor (VEGF) receptor, fibroblast growth factor (FGF)-1 receptor, neuregulin, and brain-derived neurotrophic factor (BDNF) in the acellular matrix and submucosa of the pigs'bladders were determined through the reverse transcription-polymerase chain reaction (PCR). A 5 mm X 5 mm square was excised from the penile TA of nine rabbits. The defective TA was then covered in porcine BAM. Equal numbers of animals were sacrificed and histochemically examined at 2, 4 and 6 months after implantation.</p><p><b>RESULTS</b>SEM of the BAM showed collagen fibers with many pores. VEGF receptor, FGF-1 receptor and neuregulin mRNA were expressed in the porcine BAM; BDNF mRNA was not detected. Two months after implantation, the graft sites exhibited excellent healing without contracture, and the fusion between the graft and the neighboring normal TA appeared to be well established. There were no significant histological differences between the implanted tunica and the normal control tunica at 6 months after implantation.</p><p><b>CONCLUSION</b>The porcine BAM graft resulted in a structure which was sufficiently like that of the normal TA. This implantation might be considered applicable to the reconstruction of the TA in conditions such as trauma or Peyronie's disease.</p>