Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population

Jadeja, Shahnawaz D.; Vaishnav, Jayvadan; Bharti, Ankit H

doi:10.3389/fimmu.2021.801724

Cited by 7 publications

(6 citation statements)

References 60 publications

(77 reference statements)

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“…49,50 Patients with Vitiligo have a poor response to ER stress due to a deficiency in their melanocytes that exacerbates inflammation. 51,52 In this study, the effect of LSDV on ER stress-mediated apoptosis and autophagy was not adequately determined. Further research on ER stress-induced apoptosis and degradation may provide new insights into LSDV-infected cellular processes.…”

Section: Discussionmentioning

confidence: 89%

“…Keratinization disorders and Keratosis linearis with Ichthyosis Congenita and Sclerosing Keratoderma syndrome (KLICK syndrome) are caused by ER stress that activates UPR signaling and promotes these disorders 49,50 . Patients with Vitiligo have a poor response to ER stress due to a deficiency in their melanocytes that exacerbates inflammation 51,52 . In this study, the effect of LSDV on ER stress‐mediated apoptosis and autophagy was not adequately determined.…”

Section: Discussionmentioning

confidence: 92%

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Emerging evidence for poxvirus‐mediated unfolded protein response: Lumpy skin disease virus maintains self‐replication by activating PERK and IRE1 signaling

et al. 2023

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The monkeypox epidemic has attracted global attention to poxviruses. The cytoplasmic replication of poxviruses requires extensive protein synthesis, challenging the capacity of the endoplasmic reticulum (ER). However, the role of the ER in the life cycle of poxviruses is unclear. In this study, we demonstrate that infection with the lumpy skin disease virus (LSDV), a member of the poxvirus family, causes ER stress in vivo and in vitro, further facilitating the activation of the unfolded protein response (UPR). Although UPR activation aids in the restoration of the cellular environment, its significance in the LSDV life cycle remains unclear. Furthermore, the significance of ER imbalance for viral replication is also unknown. We show that LSDV replication is hampered by an unbalanced ER environment. In addition, we verify that the LSDV replication depends on the activation of PERK‐eIF2α and IRE1‐XBP1 signaling cascades rather than ATF6, implying that global translation and reduced XBP1 cleavage are deleterious to LSDV replication. Taken together, these findings indicate that LSDV is involved in the repression of global translational signaling, ER chaperone transcription, and ATF6 cleavage from the Golgi into the nucleus, thereby maintaining cell homeostasis; moreover, PERK and IRE1 activation contribute to LSDV replication. Our findings suggest that targeting UPR elements may be applied in response to infection from LSDV or even other poxviruses, such as monkeypox.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 92%

Emerging evidence for poxvirus‐mediated unfolded protein response: Lumpy skin disease virus maintains self‐replication by activating PERK and IRE1 signaling

et al. 2023

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“…Keratinization disorders and Keratosis linearis with Ichthyosis Congenita and Sclerosing Keratoderma syndrome (KLICK syndrome) are caused by ER stress that activates UPR signaling and promotes these disorders (51, 52). Patients with Vitiligo have a poor response to ER stress due to a deficiency in their melanocytes that exacerbates inflammation (53, 54). In this study, the effect of LSDV on ER stress-mediated apoptosis and autophagy was not adequately determined.…”

Section: Discussionmentioning

confidence: 99%

Emerging Evidence for Poxvirus-Mediated Unfolded Protein Response: Lumpy Skin Disease Virus Maintains Self-replication by Activating PERK and IRE1

Tan¹,

Liu²,

Yang³

et al. 2022

Preprint

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The cytoplasmic replication of poxviruses requires extensive protein synthesis, challenging the capacity of the endoplasmic reticulum (ER). However, the role of the ER in the life cycle of poxviruses is unclear. In this study, we demonstrate that infection with the lumpy skin disease virus (LSDV), a poxvirus, causes ER stress in vivo and in vitro, further facilitating the activation of the unfolded protein response (UPR). Although UPR activation aids in the restoration of the cellular environment, its significance in the LSDV life cycle remains unclear. Furthermore, the role of ER imbalance for viral replication is also unknown. We show that LSDV replication is hampered by an unbalanced ER environment. In addition, we verify that the LSDV replication depends on the activation of PERK-eIF2α and IRE1-XBP1 signaling cascades rather than ATF6, implying that global translation and XBP1 cleavage are deleterious to LSDV replication. Our findings suggest that LSDV engages all UPR signaling sensors, and that activation of PERK and IRE1 sensors is indispensable to maintaining its own replication.

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“… 48 In addition, XBP1 increases the expression of immune mediators such as IL-6 and IL-8 as a result of ER stress in melanocytes; 49 meanwhile, recent study revealed that XBP1 is involved in the differentiation of Th17 cells and elevated the level of IL-17A in vitiligo. 50 Activation of the protein kinase R-like endoplasmic reticulum kinase-eukaryotic translation initiation factor 2α (PERK-eIF2α) and inositol-requiring enzyme 1 alpha-X-box-binding protein 1 (IRE1α-XBP1) pathways is of great importance for the production of CXCL16 induced by H 2 O 2 in keratinocytes. 18 Previous studies suggest that HMGB1 promotes the secretion of CXCL16 from keratinocytes by binding to RAGE and activating the endoplasmic reticulum kinase (ERK) and nuclear factor-κB (NF-κB) signaling pathways.…”

Section: Role Of Hmgb1 In the Oxidative Stress-mediated Development O...mentioning

confidence: 99%

Role of HMGB1 in Vitiligo: Current Perceptions and Future Perspectives

Wei¹,

Pan²,

Wang³

et al. 2022

CCID

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Vitiligo is a chronic depigmenting disorder of the skin and mucosa caused by the destruction of epidermal melanocytes. Although the exact mechanism has not been elucidated, studies have shown that oxidative stress plays an important role in the pathogenesis of vitiligo. High mobility group box protein B1 (HMGB1) is a major nonhistone protein and an extracellular proinflammatory or chemotactic molecule that is actively secreted or passively released by necrotic cells. Recent data showed that HMGB1 is overexpressed in both blood and lesional specimens from vitiligo patients. Moreover, oxidative stress triggers the release of HMGB1 from keratinocytes and melanocytes, indicating that HMGB1 may participate in the pathological process of vitiligo. Overall, this review mainly focuses on the role of HMGB1 in the potential mechanisms underlying vitiligo depigmentation under oxidative stress. In this review, we hope to provide new insights into vitiligo pathogenesis and treatment strategies.

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Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population

Cited by 7 publications

References 60 publications

Emerging evidence for poxvirus‐mediated unfolded protein response: Lumpy skin disease virus maintains self‐replication by activating PERK and IRE1 signaling

Emerging evidence for poxvirus‐mediated unfolded protein response: Lumpy skin disease virus maintains self‐replication by activating PERK and IRE1 signaling

Emerging Evidence for Poxvirus-Mediated Unfolded Protein Response: Lumpy Skin Disease Virus Maintains Self-replication by Activating PERK and IRE1

Role of HMGB1 in Vitiligo: Current Perceptions and Future Perspectives

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