Last update 19 Sep 2024

MZB1

Last update 19 Sep 2024

Basic Info

Synonyms

HSPC190, marginal zone B and B1 cell specific protein, Marginal zone B- and B1-cell-specific protein

+ [10]

Introduction

Acts as a hormone-regulated adipokine/pro-inflammatory cytokine that is implicated in causing chronic inflammation, affecting cellular expansion and blunting insulin response in adipocytes. May have a role in the onset of insulin resistance. Associates with immunoglobulin M (IgM) heavy and light chains and promotes IgM assembly and secretion. May exert its effect by acting as a molecular chaperone or as an oxidoreductase as it displays a low level of oxidoreductase activity (By similarity). Isoform 2 may be involved in regulation of apoptosis. Helps to diversify peripheral B-cell functions by regulating Ca(2+) stores, antibody secretion and integrin activation.

Drugs associated with MZB1

LCC-03

Target

MZB1 x SERP1

Mechanism

MZB1 stimulators [+1]

Active Org.

Taipei Medical University

Originator Org.

Taipei Medical University

Active Indication

Neoplasms

Inactive Indication-

Drug Highest PhaseDiscovery

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

NKP-2235

Target

MZB1 x SERP1

Mechanism

MZB1 stimulators [+1]

Active Org.-

Originator Org.

Niiki Pharma, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

HG-1160

Target

MZB1

Mechanism

MZB1 modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Neoplasms

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MZB1

100 Translational Medicine associated with MZB1

0 Patents (Medical) associated with MZB1

Literatures (Medical) associated with MZB1

01 Aug 2024·Kidney International

Evaluation of non-invasive biomarkers of kidney allograft rejection in a prospective multicenter unselected cohort study (EU-TRAIN)

Article

Author: Randoux-Lebrun, Christine ; Dragun, Duska ; Lefaucheur, Carmen ; Moreso, Francesc ; Demotes, Jacques ; Legendre, Christophe ; Raynaud, Marc ; Berney, Thierry ; Halleck, Fabian ; Racapé, Maud ; Villard, Jean ; Heidecke, Harald ; Le Mai, Hoa ; Aubert, Olivier ; Catar, Rusan Ali ; Gourraud, Pierre-Antoine ; Crespo, Elena ; Budde, Klemens ; Nguyen, Thi-Van-Ha ; Papuchon, Emmanuelle ; Bestard, Oriol ; Elias, Michelle ; Potena, Luciano ; Papalois, Vassilios ; Goutaudier, Valentin ; Girardin, François ; Philippe, Aurélie ; Loupy, Alexandre ; Yaiche, Sarhan ; Vicaut, Éric ; Brouard, Sophie ; Danger, Richard ; Taupin, Jean-Luc ; Bouton, Didier ; Zaidan, Mohamad ; Giral, Magali

Non-invasive biomarkers are promising tools for improving kidney allograft rejection monitoring, but their clinical adoption requires more evidence in specifically designed studies. To address this unmet need, we designed the EU-TRAIN study, a large prospective multicentric unselected cohort funded by the European Commission. Here, we included consecutive adult patients who received a kidney allograft in nine European transplant centers between November 2018 and June 2020. We prospectively assessed gene expression levels of 19 blood messenger RNAs, four antibodies targeting non-human leukocyte antigen (HLA) endothelial antigens, together with circulating anti-HLA donor-specific antibodies (DSA). The primary outcome was allograft rejection (antibody-mediated, T cell-mediated, or mixed) in the first year post-transplantation. Overall, 412 patients were included, with 812 biopsies paired with a blood sample. CD4 gene expression was significantly associated with rejection, while circulating anti-HLA DSA had a significant association with allograft rejection and a strong association with antibody-mediated rejection. All other tested biomarkers, including AKR1C3, CD3E, CD40, CD8A, CD9, CTLA4, ENTPD1, FOXP3, GZMB, ID3, IL7R, MS4A1, MZB1, POU2AF1, POU2F1, TCL1A, TLR4, and TRIB1, as well as antibodies against angiotensin II type 1 receptor, endothelin 1 type A receptor, C3a and C5a receptors, did not show significant associations with allograft rejection. The blood messenger RNAs and non-HLA antibodies did not show an additional value beyond standard of care monitoring parameters and circulating anti-HLA DSA to predict allograft rejection in the first year post-transplantation. Thus, our results open avenues for specifically designed studies to demonstrate the clinical relevance and implementation of other candidate non-invasive biomarkers in kidney transplantation practice.

01 Jun 2024·Cellular Signalling

MZB1 regulates cellular proliferation, mitochondrial dysfunction, and inflammation and targets the PI3K-Akt signaling pathway in acute pancreatitis

Article

Author: Xiang, Xuelian ; Tang, Guodu ; Xu, Mengtao ; Feng, Yong ; Liu, Li

BACKGROUNDAcute pancreatitis (AP) is a pathological condition characterized by the premature release and activation of trypsinogens and other enzyme precursors. In severe cases, the mortality rates are in the range of 20-30% and may even be as high as 50%. Though various prophylaxes are available for AP, the mechanism of its progression is unclear. Marginal zone B and B-1 cell-specific protein 1 (MZB1) is found in the endoplasmic reticulum (ER) where it is expressed exclusively in the B cells there. MZB1 promotes proliferation, inhibits apoptosis, invasion, and inflammation, and mitigates mitochondrial damage in cells. However, the importance of MZB1 in AP has not yet been determined.METHODSDifferentially expressed genes (DEGs) between healthy pancreatic cells and those affected by AP were identified using datasets from Gene Expression Omnibus (GEO) datasets. Relative differences in MZB1 expression between normal and diseased tissues and cells were validated in vivo using a rat AP model induced with 4% (w/v) sodium taurocholate and in vitro using the AR42J rat pancreatic cell line exposed to caerulein (CAE). Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2`-deoxyuridine (EdU) assays were performed to detect and compare normal and pathological cell proliferation. Flow cytometry was employed to assess and compare cellular apoptosis. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB) were applied to evaluate the apoptotic factors Bax and Bcl. The inflammatory factors interleukin (IL)-6 and IL-1β were quantified using Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR techniques. Mitochondrial function was evaluated using assays for reactive oxygen species (ROS) and tetramethylrhodamine methyl ester (TMRM). WB and qRT-PCR were utilized to measure the expression levels of the PI3K-Akt signaling pathway, followed by a rescue experiment involving the inhibitor of wortmannin.RESULTSMZB1 was upregulated in the AP cases screened from the GEO datasets, the rat AP model, and the AR42J cells exposed to CAE. Overexpression of MZB1 enhanced the growth and supressed the cell death of AR42J cells while also activating the PI3K-Akt signaling pathway. MZB1 knockdown led to mitochondrial dysfunction and exacerbated inflammation. The rescue experiment demonstrated that MZB1 enhanced proliferation and inhibited apoptosis, mitochondrial dysfunction, and inflammation in pancreatic cells through the PI3K-Akt pathway.CONCLUSIONSAP cells and tissues exhibited markedly elevated levels of MZB1 expression compared to their healthy counterparts. MZB1 overexpression promoted proliferation and supressed apoptosis, mitochondrial dysfunction, and inflammation in pancreatic cells through the positive regulation of the PI3K-Akt signaling pathway.

01 Jun 2024·Mucosal Immunology

MZB1-mediated IgA secretion suppresses the development and progression of colorectal cancer triggered by gut inflammation

Article

Author: Lu, Chunhui ; Luan, Yingying ; Wang, Ji-Yang ; Lu, Qing ; Cui, Chaoqun ; Liu, Jie ; Feng, Xiaoqian ; Hase, Koji ; Dong, Lulu ; Tang, Yue ; Hu, Ziying ; Yu, Meiping ; Shinkura, Reiko ; Zhang, Runyun ; Wen, Zichao

Colorectal cancer (CRC) ranks among the top causes of mortality globally. Gut inflammation is one crucial risk factor that augments CRC development since patients suffering from inflammatory bowel disease have an increased incidence of CRC. The role of immunoglobulin (Ig)A in maintaining gut homeostasis and preventing inflammation has been well established. Our earlier work demonstrated that the marginal zone and B1 cell-specific protein (MZB1) promotes gut IgA secretion and its absence results in pronounced dextran sulfate sodium salt (DSS)-induced colitis. In the present study, we explored the role of MZB1 in CRC development using the azoxymethane (AOM)/DSS-induced CRC model. We observed an increase in both the number and size of the tumor nodules in Mzb1^-/- mice compared with Mzb1^+/+ mice. The increase in CRC development and progression in Mzb1^-/- mice was associated with reduced intestinal IgA levels, altered gut flora, and more severe gut and systemic inflammation. Oral administration of the monoclonal IgA, W27, alleviated both the gut inflammation and AOM/DSS-induced CRC. Notably, cohousing Mzb1^+/+ and Mzb1^-/- mice from the 10th day after birth led to similar CRC development. Our findings underscore the pivotal role of MZB1-mediated IgA secretion in suppressing the onset and progression of CRC triggered by gut inflammation. Moreover, our study highlights the profound impact of microbiota composition, modulated by gut IgA levels, on gut inflammation. Nonetheless, establishing a direct correlation between the severity of colitis and subsequent CRC development and the presence or absence of a particular microbiota is challenging.

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MZB1

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