The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice

Koyama, Satoshi; Yoshihara, Nagisa; Takagi, Atsushi; Komiyama, Etsuko; Wada, Akino; Oka, Akira; Ikeda, Shigaku

doi:10.3390/biomedicines9070840

Cited by 6 publications

(10 citation statements)

References 14 publications

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“…According to the alle frequency aggregator project, which provides total allele frequencies from the database of Genotypes and Phenotypes, the minor allele frequency of rs142986308 is A=0.001434/280. We also reported that approximately 15% of AA patients carry a mutated CCHCR1 gene, that CCHCR1 -variant genome-edited mice and CCHCR1 knockout mice show AA-like hair loss, and that expression of keratinization-related proteins involved in hair shaft formation is altered in both mice and AA patients carrying the variant 3 7 . These findings suggest involvement of CCHCR1 in the pathogenesis of AA.…”

Section: Introductionmentioning

confidence: 83%

Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1

Koyama,

Yoshihara,

Takagi

et al. 2023

Ann Dermatol

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Background Alopecia areata (AA) is considered complex genetic and tissue-specific autoimmune disease. We recently discovered a nonsynonymous variant in the coiled-coil alpha-helical rod protein 1 ( CCHCR1 ) gene within the AA risk haplotype. And a water avoidance stress test on CCHCR1 knockout mice induced AA-like lesions. Objective To investigate the difference clinical findings of AA in patients with the CCHCR1 variant and without. Methods We conducted a retrospective analysis of the data from 142 AA patients. Among these patients, 20 (14.1%) had a variant of CCHCR1 . We evaluated the sex distribution of the patients, age at onset, distribution of the clinical types, prevalence of a positive family history of AA, prevalence of association of AA with atopic dermatitis, response to steroid therapy, and recurrence rate. We used multivariate logistic regression analysis and Fisher’s exact test for statistical analysis. We also investigate electron microscopic observations of hair samples with the CCHCR1 variant and without. Results The results showed a significant correlation between the CCHCR1 variant and the recurrence rate compared with the variant-negative group ( p =0.0072). Electron microscopy revealed abnormalities in the hair shaft structure and hair cuticle in patients with the CCHCR1 variant ( p =0.00174). Conclusion Our results suggest that AA with CCHCR1 variant is clinically characterized by a high recurrence rate and hair morphological abnormality.

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Section: Introductionmentioning

confidence: 83%

Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1

Koyama,

Yoshihara,

Takagi

et al. 2023

Ann Dermatol

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“…Recent reports have proposed that HCR is closely related to alopecia areata, psoriasis, and diabetes [ 31 , 33 , 68 ]. HCR-deficient mice showed stress-induced alopecia [ 35 ]. Since primary cilia play an important role in the development of hair follicles, the role of HCR in ciliogenesis deserves future attention.…”

Section: Discussionmentioning

confidence: 99%

“…However, the specific function of HCR in the P-body is unknown. HCR also exhibits a wide range of roles in various physiological processes, such as cell proliferation and steroid production [ 31 , 32 ], and is also associated with alopecia areata, type-2 diabetes, and squamous cell carcinoma [ 33 – 35 ]. Interestingly, HCR has been predicted to interact with a series of centrosome- and mitosis-related proteins, such as PCM1, centrin, astrin, and CEP72, which suggests that HCR may participate in PCM networks and processes related to centrosome replication and mitosis [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72

Ying

Wang

et al. 2022

BMC Biol

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Background The centrosome is one of the most important non-membranous organelles regulating microtubule organization and progression of cell mitosis. The coiled-coil alpha-helical rod protein 1 (CCHCR1, also known as HCR) gene is considered to be a psoriasis susceptibility gene, and the protein is suggested to be localized to the P-bodies and centrosomes in mammalian cells. However, the exact cellular function of HCR and its potential regulatory role in the centrosomes remain unexplored. Results We found that HCR interacts directly with astrin, a key factor in centrosome maturation and mitosis. Immunoprecipitation assays showed that the coiled-coil region present in the C-terminus of HCR and astrin respectively mediated the interaction between them. Astrin not only recruits HCR to the centrosome, but also protects HCR from ubiquitin-proteasome-mediated degradation. In addition, depletion of either HCR or astrin significantly reduced centrosome localization of CEP72 and subsequent MCPH proteins, including CEP152, CDK5RAP2, and CEP63. The absence of HCR also caused centriole duplication defects and mitotic errors, resulting in multipolar spindle formation, genomic instability, and DNA damage. Conclusion We conclude that HCR is localized and stabilized at the centrosome by directly binding to astrin. HCR are required for the centrosomal recruitment of MCPH proteins and centriolar duplication. Both HCR and astrin play key roles in keeping normal microtubule assembly and maintaining genomic stability.

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“…WS: SDS+Dfb-treated mice were placed into a plastic tank (45 cm length × 25 cm width × 25 cm height) containing warm water (35~36°C, depth of 5 to 6 cm) and removed after 2 h as previously reported ( 10 ). The procedure was repeated each weekday for 2 weeks.…”

Section: Methodsmentioning

confidence: 99%

Effects of Psychological Stress on Spontaneous Itch and Mechanical Alloknesis of Atopic Dermatitis

Zhao,

Tominaga,

Toyama

et al. 2024

Acta Derm Venereol

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Atopic dermatitis (AD), a chronic inflammatory skin disease, manifests as an intractable itch. Psychological stress has been suggested to play a role in the onset and worsening of AD symptoms. However, the pathophysiological relationships between psychological stressors and cutaneous manifestations remain unclear. To elucidate the mechanisms underlying the stress-related exacerbation of itch, we investigated the effects of water stress, restraint stress and repeated social defeat stress on itch-related scratching behaviour, mechanical alloknesis and dermatitis in male NC/Nga mice with AD-like symptoms induced by the repeated application of ointment containing Dermatophagoides farina body. NC/Nga mice with AD-like symptoms were subjected to water stress, restraint stress and repeated social defeat stress, and their scratching behaviour, sensitivity to mechanical stimuli (mechanical alloknesis) and severity of dermatitis were evaluated. Social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress showed slower improvements in or the exacerbation of AD-like symptoms, including dermatitis and itch. In the mechanical alloknesis assay, the mechanical alloknesis scores of social defeat stress+ Dermatophagoides farina body-treated mice exposed to stress were significantly higher than those of non-exposed social defeat stress+ Dermatophagoides farina body- and social defeat stress-treated mice. These results suggest that psychological stress delays improvements in dermatitis by exacerbating itch hypersensitivity in AD.

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The Alopecia Areata Phenotype Is Induced by the Water Avoidance Stress Test In cchcr1-Deficient Mice

Cited by 6 publications

References 14 publications

Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1

Clinical Findings, Response to Steroid Treatment, and Recurrence Rate in Alopecia Areata Patients with or without a Nonsynonymous Variant of Coiled-Coil Alpha-Helical Rod Protein 1

CCHCR1-astrin interaction promotes centriole duplication through recruitment of CEP72

Effects of Psychological Stress on Spontaneous Itch and Mechanical Alloknesis of Atopic Dermatitis

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