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Last update 08 May 2025

ZG16

Last update 08 May 2025

Basic Info

Synonyms

hZG16, JCLN, JCLN1

+ [5]

Introduction

May play a role in protein trafficking. May act as a linker molecule between the submembranous matrix on the luminal side of zymogen granule membrane (ZGM) and aggregated secretory proteins during granule formation in the TGN.

Drugs associated with ZG16

HG-1319

Target

ZG16

Mechanism

ZG16 gene modulators

Active Org.-

Originator Org.

Human Genome Sciences, Inc.

Active Indication-

Inactive Indication

Immune System Diseases [+3]

Drug Highest PhasePending

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with ZG16

100 Translational Medicine associated with ZG16

0 Patents (Medical) associated with ZG16

Literatures (Medical) associated with ZG16

01 Nov 2024·International Immunopharmacology

ZG16 impacts gut microbiota-associated intestinal inflammation and pulmonary mucosal function through bacterial metabolites

Article

Author: Zhang, Ying ; Yang, Guiwen ; Li, Yingjia ; Meng, Guangxun ; Wang, Yao ; Li, Hua ; Chen, Xinping ; Sun, Yaqi ; Chen, Yixin ; Zhang, Yonghuan

Zymogen granule 16 (ZG16) is a secretory glycoprotein found in zymogen granules, which also plays an important role in colorectal inflammation and cancer. Herein, a ZG16 gene knock-out (ZG16^-/-) mouse line was established and we found that ZG16 deletion damaged the intestinal mucosal barrier and gut microbiota, which resulted in low-level inflammation and further promoted the development of ulcerative colitis and inflammation-related colorectal cancer. Meanwhile, a metabolomics analysis on mouse feces showed that the metabolites significantly differed between ZG16^-/- and WT mice, which were important mediators of host-microbiota communication and may impact the pulmonary inflammation of mice. Indeed, ZG16^-/- mice showed more severe inflammation in a bronchial asthma model. Taken together, the results demonstrate that ZG16 plays a pivotal role in inhibiting inflammation and regulating immune responses in colorectum and lung of experimental animals, which may provide a better understanding of the underlying mechanism of human inflammatory diseases associated with ZG16.

21 Oct 2024·Oncogene

ZG16 enhances the maturation of dendritic cells via induction of CD40 and contributes to the antitumor immunity in pancreatic cancer

Article

Author: Li, Ling ; Zhang, Mingzhi ; Li, Yizhen ; Nan, Manman ; Meng, Hui ; Ding, Yi

Dendritic cells (DCs) are critical mediators of antigen priming and T-cell activation. Zymogen granule protein 16 (ZG16) is demonstrated as an anti-oncogene in T-cell mediated antitumor immunity, but its effect on DCs is largely unknown. Herein, we wonder whether ZG16 affects the activation of DCs in pancreatic cancer. Firstly, the increased ZG16 expression was observed during the maturation of DCs derived from mouse bone marrow or human peripheral blood. Then, overexpression of ZG16 or exogenous introduction of recombinant ZG16 protein induced the expression of MHC II, CD86, CD84, and CCR7 on the surface of DCs, thereby facilitating the secretion of proinflammatory mediators IL-1β, IL-6, TNF-α, and IL-12/p70, supporting the promoting effect of ZG16 on DC maturation. By establishing the subcutaneous and orthotopic mouse models of pancreatic cancer, we confirmed that intraperitoneal injection of recombinant ZG16 protein (Re-mZG16) could induce tumor regression by stimulating DC maturation and enhancing antitumor responses of CD4 + , CD8 + , PD-1 + , and Ctla4+ cells. Besides, Re-mZG16 in combination with gemcitabine showed a synergistic effect in the treatment of pancreatic cancer. Mechanistically, we demonstrated that ZG16 inhibited the ubiquitination and degradation of CD40, which depended on the lectin domain of ZG16. In conclusion, this study provided a novel insight into the role of ZG16-CD40 axis in DC-based immunotherapy for pancreatic cancer.

01 Aug 2024·Advanced Science

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2‐VSIR Axis in Glycogen Storage Disease

Article

Author: Jiang, Xun ; Lu, Yiyun ; Chen, Huan ; Zhang, Shaojun ; Wang, Yichao ; Zeng, Hanshi ; Zeng, Xiaolu ; Zhong, Xuemei ; Zeng, Liang ; Shen, Huiqing ; Zhang, Yuxin ; Zheng, Guilang ; Jin, Cuiyuan ; Zhang, Xuchao ; Xie, Jing ; Mao, Ren ; He, Jun ; Huang, Siyuan ; Chen, Yongxin ; Wu, Jiaxing ; Zeng, Zhaoyang ; Jin, Gulei ; Liu, Suling ; Tang, Qing ; Lan, Jiaoli ; Gong, Sitang ; Zhang, Huiqiong ; Cao, Aihua ; Xu, Wanfu ; Xiao, Yuan ; Sun, Yueyu ; Wang, Ying ; Wang, Yifei ; Hu, Yan ; Xie, Xiaoli ; Su, Zexiong ; Geng, Lanlan ; Wang, Chun ; Liu, Yumei ; Guo, Yuxiong ; Pan, Xu ; Wu, Xiaohui ; Zhang, Xiaoyan ; Ma, Ni ; Yang, Min ; Li, Zhiling ; Shi, Liyun ; Ye, Liping

AbstractPatients with glycogen storage disease type Ib (GSD‐Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD‐Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo‐polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single‐cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper‐activation of the CCL4L2‐VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD‐Ib. Collectively, the microbiota‐driven pathomechanism of IBD is demonstrated in GSD‐Ib and revealed the active role of the CCL4L2‐VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2‐VISR axis may represent a potential therapy for GSD‐associated IBD.

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ZG16

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