Twist1 Contributes to the Maintenance of Some Biological Properties of Dermal Papilla Cells in vitro by Forming a Complex With Tcf4 and ß-Catenin.

OBJECTIVE: During hair follicle regeneration, hair follicle stem cells (HFSCs) are regulated by signals from dermal papilla cells (DPCs). Previously we found that Tcf4 could promote the proliferation of DPCs. In this study, we focused on whether and how the biological properties of Tcf4-induced DPCs were regulated by Twist1. METHODS: Twist1 was overexpressed or knocked down in DPCs following different adenovirus or lentivirus infection. Phase-contrast microscopy was used to observe the agglutinative growth of DPCs. The CCK-8 assay was used to test the proliferation of DPCs. Western blot and qPCR experiments were used to determine the expression of HGF, IGF-1, VEGF, c-myc, survivin, and CyclinD1 in DPCs. ELISAs were used to test the growth factors secreted by DPCs. Conditional medium culture was used to detect the inductive ability of DPCs. Co-immunoprecipitation and immunofluorescence were used to test the binding of Twist1, Tcf4, and ß-catenin in DPCs. Immunofluorescence was also used to test the expression of Twist1, Tcf4, and KRT15 in hair follicles. RESULTS: Twist1 induced DPC agglutinative growth and proliferation. Twist1 upregulated the expression of downstream target genes downstream of Tcf4, c-myc, survivin, in Tcf4-induced DPCs, as well as the expression and secretion of growth factors HGF, IGF-1, VEGF, which had the ability to induce hair follicle growth. The conditional medium from Twist1-treated DPCs increased the expression of KRT40 and MSX2 in HaCaT cells. Twist1 and Tcf4 co-localized in DPCs both in vitro and in vivo. Anti-Twist1 precipitated Tcf4 and ß-catenin. CONCLUSION: These results indicate that Tcf4 and Twist1 play a synergistic role in regulating the hair follicle induction ability of DPCs. Twist1 functions by forming a ternary complex with Tcf4 and ß-catenin. Thus, we report new data that elucidate whether and how Twist1 regulates some biological properties of DPCs.

Author Correction: MAD2B acts as a negative regulatory partner of TCF4 on proliferation in human dermal papilla cells.

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MAD2B acts as a negative regulatory partner of TCF4 on proliferation in human dermal papilla cells.

Dermal papilla cells (DPCs) are important components of hair follicles and play a critical role in hair follicle development. However, the mechanisms by which DPCs induce hair follicle development remain unclear. In the present study, we identified the mitotic arrest deficient protein MAD2B as a modifier of DPCs. Overexpression of MAD2B inhibited DPC aggregative growth and proliferation induced by the Wnt signaling activator T cell factor 4 (TCF4), and decreased TCF4-induced expression and the release of hair growth-related cytokines, including hepatocyte growth factor, insulin-like growth factor-1, and vascular endothelial growth factor in DPCs. In contrast, knockdown of MAD2B promoted TCF4-induced DPC proliferation, but did not affect the expression and secretion of cytokines by TCF4-induced DPCs. These results suggest a functional antagonism between MAD2B and TCF4 in DPC-induced hair follicle development. Mechanistically, MAD2B physically interacted with TCF4 to repress TCF4 transcriptional activity via ß-catenin mediation, leading to reduced ß-catenin/TCF4-dependent transactivation and Wnt signaling activity. These results demonstrate, for the first time, that MAD2B plays a negative role in TCF4-induced DPC growth and proliferation.

Illness perception in patients with androgenetic alopecia and alopecia areata in China.

OBJECTIVE: The aim of the present study was to provide more information on the role of illness perception in patients with androgenetic alopecia (AGA) and those with alopecia areata (AA), and to further investigate the relationship of illness perception with psychological disorders and dermatological QoL. METHODS: The study included 342 patients who were diagnosed with AGA (n=212) or AA (n=130) for the first time at our institution between October 2013 and December 2014. All patients were surveyed before clinical examination by several questionnaires including the Brief Illness Perception, Self-rating Depression Scale, Self-rating Anxiety Scale, and Dermatology Life Quality Index (DLQI). RESULTS: In the AGA patients, the illness perception and QoL were low, whereas the prevalence of clinical depression and anxiety was higher compared to the AA patients. Illness perception was associated with psychological distress and low QoL in both groups, and some illness perception dimensions were found to be significant predictors of the DLQI scores. CONCLUSION: Illness perception plays an important role in AGA and AA patients, and is associated with psychological distress and low QoL. The identification of critical components of illness perception in alopecia patients could help to understand alopecia specificities, to design consultations and interventions according to the perception, and to improve physical and mental outcomes as well as QoL in alopecia patients.

Reliability and validity assessment of the revised Symptom Checklist 90 for alopecia areata patients in China.

No study has tested the reliability and validity of the revised Symptom Checklist 90 (SCL-90-R) for patients with alopecia areata (AA), and few have used it to evaluate the mental health of AA patients. To assess the psychological status in Chinese AA patients using the SCL-90-R, and to evaluate its reliability and validity, the psychological status of 168 patients and 100 controls was evaluated with the Chinese-version SCL-90-R. From this study, we found that The Global Severity Index and nine subscale scores on the SCL-90-R were significantly higher in AA patients than that in the controls. Moreover, The Global Severity Index and nine subscale scores on the SCL-90-R were associated with disease duration, age of onset, sex and type of AA. In addition, the SCL-90-R presented good internal consistency (whole scale α = 0.98 and split-half coefficient = 0.95). The intercorrelations between the nine subscales and their correlations with the total scale were 0.58-0.93. Factor analysis produced 22 factors with eigenvalues more than 1.0; the first factor explained 33.88% of the variance. Only hostility and paranoid ideation merged into one factor. Taken together, our data indicated that Chinese AA patients demonstrate greater psychopathology than healthy controls. The SCL-90-R can be used to assess global psychological distress in AA patients with good reliability and validity.