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Keywords = Erdr1

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19 pages, 7578 KiB  
Article
Erythroid Differentiation Regulator 1 as a Regulator of Neuronal GSH Synthesis
by Wattanaporn Bhadhprasit, Chisato Kinoshita, Nobuko Matsumura and Koji Aoyama
Antioxidants 2024, 13(7), 771; https://doi.org/10.3390/antiox13070771 - 26 Jun 2024
Cited by 2 | Viewed by 1787
Abstract
Erythroid differentiation regulator 1 (Erdr1) is a cytokine known to play important roles in cell survival under stressful conditions, maintenance of cellular growth homeostasis, and activation of the immune system. However, the impact of Erdr1 on neurons remains undefined. In this study, we [...] Read more.
Erythroid differentiation regulator 1 (Erdr1) is a cytokine known to play important roles in cell survival under stressful conditions, maintenance of cellular growth homeostasis, and activation of the immune system. However, the impact of Erdr1 on neurons remains undefined. In this study, we present novel evidence that Erdr1 plays a role in regulating glutathione (GSH) synthesis via glutamate transporter-associated protein 3-18 (GTRAP3-18), an anchor protein in the endoplasmic reticulum that holds excitatory amino acid carrier 1 (EAAC1) in neurons. Both DNA microarray and quantitative real-time PCR analyses revealed an approximately 2-fold increase in Erdr1 levels in the hippocampus of GTRAP3-18-deficient mice compared to those of wild-type mice. Knockdown of Erdr1 in vitro resulted in a decrease in GTRAP3-18 levels, leading to an increase in EAAC1 expression and intracellular GSH levels, and subsequently, cytoprotective effects against oxidative stress. Our findings shed light on the regulatory mechanisms involving Erdr1, GTRAP3-18, EAAC1, and GSH in the context of neuronal defense against oxidative stress. Understanding the intricate interplay among these molecules may pave the way for the development of promising therapeutic strategies for neurodegenerative disorders. Full article
(This article belongs to the Section Natural and Synthetic Antioxidants)
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9 pages, 1966 KiB  
Article
Erythroid Differentiation Regulator 1 Strengthens TCR Signaling by Enhancing PLCγ1 Signal Transduction Pathway
by Myun Soo Kim, Dongmin Park, Sora Lee, Sunyoung Park, Kyung Eun Kim, Tae Sung Kim, Hyun Jeong Park and Daeho Cho
Int. J. Mol. Sci. 2022, 23(2), 844; https://doi.org/10.3390/ijms23020844 - 13 Jan 2022
Cited by 2 | Viewed by 2334
Abstract
Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected [...] Read more.
Erythroid differentiation regulator 1 (Erdr1) has previously been reported to control thymocyte selection via TCR signal regulation, but the effect of Erdr1 as a TCR signaling modulator was not studied in peripheral T cells. In this report, it was determined whether Erdr1 affected TCR signaling strength in CD4 T cells. Results revealed that Erdr1 significantly enhanced the anti-TCR antibody-mediated activation and proliferation of T cells while failing to activate T cells in the absence of TCR stimulation. In addition, Erdr1 amplified Ca2+ influx and the phosphorylation of PLCγ1 in CD4 T cells with the TCR stimuli. Furthermore, NFAT1 translocation into nuclei in CD4 T cells was also significantly promoted by Erdr1 in the presence of TCR stimulation. Taken together, our results indicate that Erdr1 positively modulates TCR signaling strength via enhancing the PLCγ1/Ca2+/NFAT1 signal transduction pathway. Full article
(This article belongs to the Special Issue The Many Facets of the Regulation of TCR Signaling)
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12 pages, 3017 KiB  
Article
Involvement of the MxtR/ErdR (CrbS/CrbR) Two-Component System in Acetate Metabolism in Pseudomonas putida KT2440
by Tania Henriquez and Heinrich Jung
Microorganisms 2021, 9(8), 1558; https://doi.org/10.3390/microorganisms9081558 - 22 Jul 2021
Cited by 5 | Viewed by 3429
Abstract
MxtR/ErdR (also called CrbS/CrbR) is a two-component system previously identified as important for the utilization of acetate in Vibrio cholerae and some Pseudomonas species. In addition, evidence has been found in Pseudomonas aeruginosa for a role in regulating the synthesis and expression, respectively, [...] Read more.
MxtR/ErdR (also called CrbS/CrbR) is a two-component system previously identified as important for the utilization of acetate in Vibrio cholerae and some Pseudomonas species. In addition, evidence has been found in Pseudomonas aeruginosa for a role in regulating the synthesis and expression, respectively, of virulence factors such as siderophores and RND transporters. In this context, we investigated the physiological role of the MxtR/ErdR system in the soil bacterium Pseudomonas putida KT2440. To that end, mxtR and erdR were individually deleted and the ability of the resulting mutants to metabolize different carbon sources was analyzed in comparison to wild type. We also assessed the impact of the deletions on siderophore production, expression of mexEF-oprN (RND transporter), and the biocontrol properties of the strain. Furthermore, the MxtR/ErdR-dependent expression of putative target genes and binding of ErdR to respective promoter regions were analyzed. Our results indicated that the MxtR/ErdR system is active and essential for acetate utilization in P. putida KT2440. Expression of scpC, pp_0354, and acsA-I was stimulated by acetate, while direct interactions of ErdR with the promoter regions of the genes scpC, pp_0354, and actP-I were demonstrated by an electromobility shift assay. Finally, our results suggested that MxtR/ErdR is neither involved in regulating siderophore production nor the expression of mexEF-oprN in P. putida KT2440 under the conditions tested. Full article
(This article belongs to the Special Issue Complex Signal Transduction Systems in Bacteria)
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10 pages, 5509 KiB  
Article
Erythroid Differentiation Regulator 1 Ameliorates Collagen-Induced Arthritis via Activation of Regulatory T Cells
by Myun Soo Kim, Sora Lee, Sunyoung Park, Kyung Eun Kim, Hyun Jeong Park and Daeho Cho
Int. J. Mol. Sci. 2020, 21(24), 9555; https://doi.org/10.3390/ijms21249555 - 15 Dec 2020
Cited by 4 | Viewed by 2629
Abstract
Erythroid differentiation regulator 1 (Erdr1) has been identified as an anti-inflammatory factor in several disease models, including collagen-induced arthritis (CIA), but its exact mechanisms are still not fully understood. Here, the involvement of regulatory T (Treg) cells in Erdr1-improved CIA was investigated. In [...] Read more.
Erythroid differentiation regulator 1 (Erdr1) has been identified as an anti-inflammatory factor in several disease models, including collagen-induced arthritis (CIA), but its exact mechanisms are still not fully understood. Here, the involvement of regulatory T (Treg) cells in Erdr1-improved CIA was investigated. In the CIA model, Erdr1 was confirmed to reduce collagen-specific IgM in plasma and plasma cells in draining lymph nodes. Importantly, the downregulated Treg cell ratio in draining lymph nodes from CIA mice was recovered by Erdr1 treatment. In addition, administration of Erdr1 improved the CIA score and joint tissue damage, while it revealed no effect in Treg cell-depleted CIA mice, indicating that Treg cells mediate the therapeutic effects of Erdr1 in the CIA model. Results from in vitro experiments also demonstrated that Erdr1 significantly induced Treg cell differentiation and the expression of Treg activation markers, including CD25, CD69, and CTLA4 in CD4+Foxp3+ cells. Furthermore, Erdr1-activated Treg cells dramatically suppressed the proliferation of responder T cells, suggesting that they are functionally active. Taken together, these results show that Erdr1 induces activation of Treg cells and ameliorates rheumatoid arthritis via Treg cells. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Rheumatoid Arthritis)
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10 pages, 976 KiB  
Review
The Role of Erythroid Differentiation Regulator 1 (ERDR1) in the Control of Proliferation and Photodynamic Therapy (PDT) Response
by Sunyoung Park, Kyung Eun Kim, Hyun Jeong Park and Daeho Cho
Int. J. Mol. Sci. 2020, 21(7), 2603; https://doi.org/10.3390/ijms21072603 - 9 Apr 2020
Cited by 4 | Viewed by 4354
Abstract
Erythroid differentiation regulator 1 (ERDR1) was newly identified as a secreted protein that plays an essential role in maintaining cell growth homeostasis. ERDR1 enhances apoptosis at high cell densities, leading to the inhibition of cell survival. Exogenous ERDR1 treatment decreases cancer cell proliferation [...] Read more.
Erythroid differentiation regulator 1 (ERDR1) was newly identified as a secreted protein that plays an essential role in maintaining cell growth homeostasis. ERDR1 enhances apoptosis at high cell densities, leading to the inhibition of cell survival. Exogenous ERDR1 treatment decreases cancer cell proliferation and tumor growth as a result of increased apoptosis via the regulation of apoptosis-related gene expression. Moreover, ERDR1 plays a pivotal role in skin diseases; ERDR1 expression in actinic keratosis (AK) is negatively correlated with the increase in apoptosis. Because of its high specificity and efficiency, photodynamic therapy (PDT) is a common therapy for patients with various skin diseases, including cancer. Many studies indicate that apoptosis is mainly induced by PDT treatment. As an apoptosis inducer, the recovery of the ERDR1 expression after PDT is correlated with good therapeutic outcomes. Here, we review recent findings that highlight the function of ERDR1 in the control of apoptosis. Thus, ERDR1 may have a role in the apoptosis regulation of target cells in the lesions, as the recovery of its expression after PDT is correlated with good therapeutic outcomes. Full article
(This article belongs to the Special Issue Skin Cancer: From Pathophysiology to Novel Therapeutic Approaches)
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13 pages, 9096 KiB  
Communication
Erythroid Differentiation Regulator 1 as a Novel Biomarker for Hair Loss Disorders
by Yu Ri Woo, Sewon Hwang, Seo Won Jeong, Dae Ho Cho and Hyun Jeong Park
Int. J. Mol. Sci. 2017, 18(2), 316; https://doi.org/10.3390/ijms18020316 - 3 Feb 2017
Cited by 5 | Viewed by 6709
Abstract
Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of [...] Read more.
Erythroid differentiation regulator 1 (Erdr1) is known to be involved in the inflammatory process via regulating the immune system in many cutaneous disorders, such as psoriasis and rosacea. However, the role of Erdr1 in various hair loss disorders remains unclear. The aim of this study was to investigate the putative role of Erdr1 in alopecias. Skin samples from 21 patients with hair loss disorders and five control subjects were retrieved, in order to assess their expression levels of Erdr1. Results revealed that expression of Erdr1 was significantly downregulated in the epidermis and hair follicles of patients with hair loss disorders, when compared to that in the control group. In particular, the expression of Erdr1 was significantly decreased in patients with alopecia areata. We propose that Erdr1 downregulation might be involved in the pathogenesis of hair loss, and could be considered as a novel biomarker for hair loss disorders. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions)
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10 pages, 977 KiB  
Review
Roles of Erythroid Differentiation Regulator 1 (Erdr1) on Inflammatory Skin Diseases
by Youn Kyung Houh, Kyung Eun Kim, Hyun Jeong Park and Daeho Cho
Int. J. Mol. Sci. 2016, 17(12), 2059; https://doi.org/10.3390/ijms17122059 - 8 Dec 2016
Cited by 14 | Viewed by 7656
Abstract
Erythroid Differentiation Regulator 1 (Erdr1) is known as a hemoglobin synthesis factor which also regulates cell survival under conditions of stress. In addition, previous studies have revealed the effects of Erdr1 on cancer progression and its negative correlation with interleukin (IL)-18, a pro-inflammatory [...] Read more.
Erythroid Differentiation Regulator 1 (Erdr1) is known as a hemoglobin synthesis factor which also regulates cell survival under conditions of stress. In addition, previous studies have revealed the effects of Erdr1 on cancer progression and its negative correlation with interleukin (IL)-18, a pro-inflammatory cytokine. Based on this evidence, the therapeutic effects of Erdr1 have been demonstrated in several inflammatory skin diseases such as malignant skin cancer, psoriasis, and rosacea. This article reviews the roles of Erdr1 in skin inflammation, suggesting that Erdr1 is a potential therapeutic molecule on inflammatory disorders. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions)
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11 pages, 1474 KiB  
Article
Therapeutic Effects of Erythroid Differentiation Regulator 1 on Imiquimod-Induced Psoriasis-Like Skin Inflammation
by Kyung Eun Kim, Younkyung Houh, Hyun Jeong Park and Daeho Cho
Int. J. Mol. Sci. 2016, 17(2), 244; https://doi.org/10.3390/ijms17020244 - 17 Feb 2016
Cited by 15 | Viewed by 7741
Abstract
Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been [...] Read more.
Psoriasis is a common skin disease accompanied by chronic inflammation. In previous studies, erythroid differentiation regulator 1 (ERDR1) was shown to have a negative correlation with proinflammatory cytokine IL-18. However, the role of ERDR1 in the inflammatory skin disease psoriasis has not been evaluated. In this study, to investigate the role of ERDR1 in psoriasis, recombinant ERDR1 was injected intraperitoneally into a psoriasis mouse model. Recombinant ERDR1 (rERDR1) significantly alleviated the symptoms of psoriasis-like skin inflammation and reduced the mRNA of various psoriasis-related markers, including keratin 14, S100A8, and Th17-related cytokines IL-17 and IL-22, suggesting that rERDR1 exerts therapeutic effects on psoriasis via the regulation of Th17 functions. Additionally, the expression of CCL20, a well-known Th17 attracting chemokine, was determined. CCL20 expression significantly decreased in the rERDR1-injected group compared with the vehicle (PBS)-injected group. CCR6 expression in the psoriatic lesional skin was also decreased by rERDR1 administration, implying the inhibition of CCR6-expressing Th17 cell chemotaxis via the downregulation of CCL20. Taken together, this study provides the first evidence that ERDR1 may be a potential therapeutic target for psoriasis. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions)
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8 pages, 1352 KiB  
Communication
Erdr1 Suppresses Murine Melanoma Growth via Regulation of Apoptosis
by Joohyun Lee, Min Kyung Jung, Hyun Jeong Park, Kyung Eun Kim and Daeho Cho
Int. J. Mol. Sci. 2016, 17(1), 107; https://doi.org/10.3390/ijms17010107 - 14 Jan 2016
Cited by 16 | Viewed by 7107
Abstract
Melanoma, one of the aggressive cancers, is known to be resistant to chemotherapy. Because of its aggressive nature, effectively inducing apoptosis is necessary to treat melanoma. Erythroid differentiation regulator 1 (Erdr1) is known to be a stress-related survival factor exhibiting anti-cancer effects in [...] Read more.
Melanoma, one of the aggressive cancers, is known to be resistant to chemotherapy. Because of its aggressive nature, effectively inducing apoptosis is necessary to treat melanoma. Erythroid differentiation regulator 1 (Erdr1) is known to be a stress-related survival factor exhibiting anti-cancer effects in several cancers. However, little is known about the functions and underlying mechanisms of Erdr1 so far. To demonstrate the effect of Erdr1 in melanoma apoptosis, recombinant murine Erdr1 was injected into mice implanted with B16F10 melanoma cells. In vivo tumor growth was significantly inhibited in mice injected with Erdr1 compared to the control. In addition, the tumor from Erdr1-injected mice showed an increased level of apoptosis. Accordingly, apoptosis-regulating factors including anti-apoptotic marker Bcl-2 and pro-apoptotic marker Bax in the tumor tissues were examined. As expected, the decreased level of Bcl-2 and increased level of Bax were detected in tumors within the mice injected with Erdr1. Based on the in vivo study, the role of Erdr1 in tumor apoptosis was further tested by incubating it with cells of the murine melanoma cell line B16F10. Erdr1-induced apoptosis in B16F10 cells was observed. Additionally, Erdr1 downregulated STAT3 activity, inhibiting apoptosis via regulation of the Bcl-2 family. Overall, data demonstrate that Erdr1 induced murine melanoma apoptosis through the regulation of Bcl-2 and Bax. These findings suggest that Erdr1 is a novel regulator of apoptosis in melanoma. Full article
(This article belongs to the Special Issue Inflammatory Skin Conditions)
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