Detrimental Role of Nerve Injury-Induced Protein 1 in Myeloid Cells under Intestinal Inflammatory Conditions

Jung, Hyun Jin; Kang, Ju‐Hee; Pak, Seongwon; Lee, Keunwook; Seong, Je Kyung; Oh, Seung Hyun

doi:10.3390/ijms21020614

Cited by 15 publications

(17 citation statements)

References 55 publications

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“… 39 Increased oxidative stress, endoplasmic reticulum (ER) stress (ERS) or NF-κB activation also enhances NINJ1 expression. 40 NINJ1 is involved in many inflammatory diseases, including diabetes mellitus, 24 nervous system inflammatory lesions, 22 intestinal inflammatory conditions, 23 and experimental autoimmune encephalomyelitis. 21 However, these previously established studies on the roles of NINJ1 in inflammation were mainly focused on NINJ1-mediated leukocyte migration, although NINJ1 can also interact with LPS and regulate Toll-like receptor 4 (TLR4) signaling.…”

Section: Discussionmentioning

confidence: 99%

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Role of NINJ1 in Gout Flare and Potential as a Drug Target

Zhang¹,

Gao²,

Fang³

et al. 2022

JIR

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To determine the role of nerve injury-induced protein 1 (NINJ1) introduced plasma membrane rupture (PMR) and damage-associated molecular patterns (DAMPs) release in the pathogenesis and progression of gout and to explore the potential of NINJ1 as a therapeutic target in gout. Methods: Both peripheral blood mononuclear cells (PBMCs) and serum sample from gout patients (n = 58) and healthy controls (n = 16) were collected and processed to NINJ1 expression, lactate dehydrogenase (LDH) detection, NINJ1 inhibition, and NINJ1 expression experiments, respectively. NINJ1 knockdown was carried out by lentivirus in a monosodium urate (MSU) induced rat model, and NINJ1 neutralizing antibody was applied in a MSU induced mouse model. Results: Our results found that NINJ1 was upregulated during a gout flare, and the resulting induction of PMR correlated with gout progression. NINJ1 knockdown significantly reduced the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activation and joint swelling in the rat model, and NINJ1 neutralizing antibody also significantly reduced gout flare in the mouse model and PBMCs. Moreover, NINJ1 expression is under NLRP3 inflammasome produced interleukin (IL)-1β control. Conclusion: These results support the notion of a pathogenic role of NINJ1 introduced PMR in gout and provide a detailed mechanism for gout pathogenesis involving inflammatory cell death and DAMPs release introduced by IL-1β. In addition, targeting NINJ1 might be a potential therapeutic approach for gout.

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Section: Discussionmentioning

confidence: 99%

“… 22 NINJ1 expression results in macrophage activation in intestinal inflammatory conditions. 23 Blocked of NINJ1 protected diabetic endothelial cells from high-glucose induced apoptosis in diabetes mellitus. 24 Besides, NINJ1 asp110ala single nucleotide polymorphism is associated with protection in leprosy nerve damage.…”

Section: Introductionmentioning

confidence: 97%

Role of NINJ1 in Gout Flare and Potential as a Drug Target

Zhang¹,

Gao²,

Fang³

et al. 2022

JIR

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“…The safety level was measured by evaluating ERK phosphorylation [ 37 ]. Dovitinib (TKI258) is an inhibitor of multiple kinases, including FGFR, VEGFR, and platelet-derived growth factor receptor (PDGFR); its efficacy has been proven in HER2-negative metastatic breast cancer (NCT00958971), and it inhibits the invasion of MDA-MB-231(SA) cells [ 38 , 39 ]. E-3810 inhibits FGFR1 , FGFR2 , CSF1R , VEGFR1 , VEGFR2 , and VEGFR3I [ 40 ].…”

Section: Targets Of Tnbc Under Active Clinical Evaluationmentioning

confidence: 99%

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

Singh

Yadav

2021

Biomedicines

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Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.

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“…To our knowledge, several pieces of research elucidate that abnormal activation of proinflammatory macrophages could lead to intestinal inflammation [34, 35]. Concomitantly, Jung et al [36] proclaimed that Ninj1 expression was significantly enhanced in the dextran sodium sulfate-induced mice intestinal inflammation models, especially on the surface of macrophages. More importantly, Ninj1-knockout mice exhibited mild clinical phenotype and pathological lesions than wild-type (WT) mice during experimental colitis.…”

Section: Roles Of Ninjurin1 Outside the Nervous Systemmentioning

confidence: 99%

“…More importantly, Ninj1-knockout mice exhibited mild clinical phenotype and pathological lesions than wild-type (WT) mice during experimental colitis. Furthermore, Jung et al [36] concluded that Ninj1 contributes to the activation of macrophages, thereby promoting the secretion of proinflammatory factors and chemokines, such as IL-1β, IL-6, and CCL2, via the TLR4-protein Kinase C δ/θ signaling pathway during the development of colitis in vivo [36]. Notably, unlike its role in the CNS, Ninj1 does not promote the infiltration of macrophages into the inflammatory lesion site, but rather promotes the activation of macrophages under the intestinal inflammatory conditions [36].…”

Section: Roles Of Ninjurin1 Outside the Nervous Systemmentioning

confidence: 99%

The Role of Ninjurin1 and Its Impact beyond the Nervous System

Liu

Wang

2020

Dev Neurosci

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Ninjurin1 (Ninj1) is a double-transmembrane cell surface protein that could promote nerve regeneration in the process of the peripheral nervous system injury and repairment. Nonetheless, the accurate function of Ninj1 in the central nervous system and outside the nervous system is not completely clear. According to the recent studies, we found that Ninj1 is also aberrantly expressed in various pathophysiological processes in vivo, including inflammation, tumorigenesis, and vascular, bone, and muscle homeostasis. These findings suggest that Ninj1 may play an influential role during these pathophysiological processes. Our review summarizes the diverse roles of Ninj1 in multiple pathophysiological processes inside and outside the nervous system. Ninj1 should be considered as an important and novel therapeutic target in certain diseases, such as inflammatory diseases and ischemic diseases. Our study provided a better understanding of Ninj1 in different pathophysiological processes and thereby provided the theoretical support for further research.

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Detrimental Role of Nerve Injury-Induced Protein 1 in Myeloid Cells under Intestinal Inflammatory Conditions

Cited by 15 publications

References 55 publications

Role of NINJ1 in Gout Flare and Potential as a Drug Target

Role of NINJ1 in Gout Flare and Potential as a Drug Target

TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy

The Role of Ninjurin1 and Its Impact beyond the Nervous System

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