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Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis 未折叠蛋白反应调节酪氨酸酶水平和黑色素生成过程中的黑色素。
IF 4.6
Journal of dermatological science
Pub Date : 2025-02-01 DOI: 10.1016/j.jdermsci.2025.01.001
Akari Yamazaki , Issei Omura , Yasunao Kamikawa , Michihiro Hide , Akio Tanaka , Masayuki Kaneko , Kazunori Imaizumi , Atsushi Saito

Background

Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.

Objective

This study investigates the regulatory mechanisms of melanin production, focusing on ER stress and the ER stress-induced response.

Methods

B16 mouse melanoma cells induced to undergo melanogenesis were treated with unfolded protein response (UPR) inhibitors or chemical chaperones, and their effects on melanogenesis were analyzed.

Results

During melanogenesis in B16 cells stimulated by alpha-melanocyte-stimulating hormone (α-MSH), ER stress and UPR activation occurred, accompanied by increased Tyrosinase protein. Reducing IRE1 and ATF6 branch activity lowered melanin levels, while chemical chaperone treatment restored melanin production and increased Tyrosinase levels.

Conclusion

UPR activation, linked to elevated Tyrosinase levels, influences melanin production during melanogenesis. Modulating UPR can regulate melanin synthesis and provides a potential new approach for treating pigmentation disorders.
背景：黑色素细胞通过合成黑色素保护人体免受紫外线辐射。酪氨酸酶是黑色素生成的关键酶，在黑色素合成过程中在内质网（ER）中积累，可能导致内质网应激。然而，与控制酪氨酸酶活性相比，调节内质网功能对黑色素合成的影响研究较少。目的：研究内质网应激和内质网应激诱导的黑色素生成调控机制。方法：采用未折叠蛋白反应（UPR）抑制剂或化学伴侣对诱导黑色素生成的B16小鼠黑色素瘤细胞进行处理，分析其对黑色素生成的影响。结果：α-MSH刺激B16细胞黑素形成过程中，内质网应激和UPR激活，酪氨酸酶蛋白升高。降低IRE1和ATF6分支活性降低黑色素水平，而化学伴侣处理恢复黑色素生成并增加酪氨酸酶水平。结论：UPR激活与酪氨酸酶水平升高有关，影响黑色素形成过程中黑色素的产生。调节UPR可以调节黑色素的合成，为治疗色素沉着疾病提供了潜在的新途径。
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引用次数: 0
Corrigendum to “The cumulative effect of compound heterozygous variants in TRPV3 caused Olmsted syndrome” [J. Dermatol. Sci. (2024) S0923-1811(24)00214-7] “TRPV3中复合杂合变异体的累积效应导致Olmsted综合征”的更正[J]。北京医学。科学。(2024) s0923 - 1811(24) 00214 - 7]。
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01 DOI: 10.1016/j.jdermsci.2024.11.003
Ran Mo , Xiaoqi Ma , Linghan Hu , Yingjian Tan , Lei Qiang , Yong Yang , Xiaoping Wang , Zhiming Chen
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
Editors choice 编辑的选择
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01 DOI: 10.1016/S0923-1811(25)00007-6
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引用次数: 0
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01
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引用次数: 0
Improvement of immunological tests for detecting autoantibodies in patients with lamina lucida-type linear IgA bullous dermatosis 改进免疫学试验，以检测透明层型线性 IgA 大疱性皮肤病患者的自身抗体。
IF 4.6
Journal of dermatological science
Pub Date : 2025-01-01 DOI: 10.1016/j.jdermsci.2024.12.001
Masahiro Tsutsumi , Hiroshi Koga , Kwesi Teye , Norito Ishii , Takekuni Nakama

Background

In the diagnosis of linear IgA bullous dermatosis (LABD), detection of IgA at the epidermal basement membrane zone and circulating IgA autoantibodies are essential. The disease has two subtypes, lamina lucida-type and sublamina densa-type, with 120 kDa LAD-1 and 97 kDa LABD97 as major autoantigens for lamina lucida-type. Normal human epidermal keratinocytes (NHEK) and HaCaT cells are widely used for immunoblotting (IB) in the diagnosis process, but they do not provide high sensitivity and semiquantitative analysis.

Objective

To develop a more sensitive and convenient method for detecting IgA antibodies in lamina lucida-type LABD patients.

Methods

The expressions of LAD-1 and LABD97 in lysates and culture supernatants from Ker-CT, HaCaT, DJM-1, and NHEK were compared. The sensitivity of IBs using concentrated culture supernatants of HaCaT and Ker-CT and ELISAs using several recombinant proteins (RPs) corresponding to BP180 ectodomain were compared using 55 sera from LABD patients.

Results

In culture supernatant, Ker-CT expressed higher amounts of LAD-1 and LABD97. IBs using concentrated culture supernatant of HaCaT and Ker-CT showed 43 % and 46 % positivity to sera from LABD patients, respectively. In ELISAs, the RP of amino acids 490–1421 of BP180 showed the highest positivity (80.0 %) among several proteins. Additionally, this ELISA showed reduced OD values in LABD and related diseases patients' sera at remission.

Conclusion

The ELISA using the RP coding amino acids 490–1421 of BP180 is useful for identifying IgA antibodies and monitoring disease activity in lamina lucida-type LABD patients.
背景：在线性IgA大疱性皮肤病（LABD）的诊断中，检测表皮基底膜区IgA和循环IgA自身抗体是必不可少的。该疾病有两种亚型，即透明层型和膜下致密型，其中120 kDa LAD-1和97 kDa LABD97是透明层型的主要自身抗原。正常人表皮角质形成细胞（NHEK）和HaCaT细胞在诊断过程中广泛用于免疫印迹（IB），但它们不能提供高灵敏度和半定量分析。目的：建立一种更灵敏、简便的检测透明层型LABD患者IgA抗体的方法。方法：比较Ker-CT、HaCaT、DJM-1和NHEK的裂解液和培养上清液中LAD-1和LABD97的表达。用55例LABD患者的血清比较HaCaT和Ker-CT的浓培养上清和BP180外结构域对应的重组蛋白（RPs）的elisa的敏感性。结果：培养上清中，Ker-CT表达较高的lad1和LABD97。使用HaCaT和Ker-CT浓缩培养上清的IBs对LABD患者血清的阳性率分别为43% %和46% %。在酶联免疫吸附试验中，BP180的490 ~ 1421氨基酸的RP在几种蛋白中阳性率最高（80.0 %）。此外，该ELISA显示，缓解期LABD及相关疾病患者血清中的OD值降低。结论：利用RP编码BP180蛋白490 ~ 1421氨基酸的酶联免疫吸附试验（ELISA）可用于荧光层型LABD患者的IgA抗体鉴定和疾病活动性监测。
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引用次数: 0
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