Transcription factor FOXC1 positively regulates SFRP1 expression in androgenetic alopecia.

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from -100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.

Volatile composition and classification of Lilium flower aroma types and identification, polymorphisms, and alternative splicing of their monoterpene synthase genes.

Lily is a well-known ornamental plant with a diversity of fragrant types. Basic information on lily floral scent compounds has been obtained for only a few accessions, and little is known about Lilium aroma types, the terpene synthase genes that may play roles in the production of key volatiles, or the range of monoterpenes that these genes produce. In this study, 41 cultivars were analyzed for volatile emissions, and a total of 46 individual volatile compounds were identified, 16 for the first time in lilies. Lily accessions were classified into six groups according to the composition of major scent components: faint-scented, cool, fruity, musky, fruity-honey, and lily. Monoterpenes were one of the main groups of volatiles identified, and attention was focused on terpene synthase (TPS) genes, which encode enzymes that catalyze the last steps in monoterpene synthesis. Thirty-two candidate monoterpene synthase cDNAs were obtained from 66 lily cultivars, and 64 SNPs were identified. Two InDels were also shown to result from variable splicing, and sequence analysis suggested that different transcripts arose from the same gene. All identified nucleotide substitution sites were highly correlated with the amounts of myrcene emitted, and InDel site 230 was highly correlated with the emission of all major monoterpenoid components, especially (E)-ß-ocimene. Heterologous expression of five cDNAs cloned from faint-scented and strong-scented lilies showed that their corresponding enzymes could convert geranyl diphosphate to (E)-ß-ocimene, α-pinene, and limonene. The findings from this study provide a major resource for the assessment of lily scent volatiles and will be helpful in breeding of improved volatile components.

Identification of critically carcinogenesis-related genes in basal cell carcinoma.

BACKGROUND: Basal cell carcinoma (BCC) is a frequent malignant tumor of skin cancers with high morbidity. The objective of this study was to identify critical genes and pathways related to the carcinogenesis of BCC and gain more insights into the underlying molecular mechanisms of BCC. MATERIALS AND METHODS: The gene expression profiles of GSE7553 and GSE103439 were downloaded from the Gene Expression Omnibus database with 19 tumors and 6 normal skin tissues. Differentially expressed genes (DEGs) were screened between BCC samples and normal tissues, followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Subsequently, protein-protein interaction (PPI) network was constructed for these DEGs, and module analysis was performed. RESULTS: A total of 313 DEGs were obtained. Among them, 222 genes were upregulated and 91 genes were downregulated. Enrichment analysis indicated that the upregulated genes were significantly enriched in cell cycle and mitosis, while the downregulated genes were mainly associated with unsaturated fatty acid metabolic process and cell differentiation. In addition, TOP2A, CDK1, and CCNB1 were identified as the top three hub genes ranked by degrees in the PPI network. Meanwhile, three subnetworks were derived, which indicated that these DEGs were significantly enriched in pathways, including "cell cycle", "extracellular matrix-receptor interaction", "basal cell carcinoma", and "hedgehog signaling pathway". CONCLUSIONS: The novel critical DEGs and pathways identified in this study may serve pivotal roles in the carcinogenesis of BCC and indicate more molecular targets for the treatment of BCC.

An investigation of crosstalk between Wnt/ß-catenin and transforming growth factor-ß signaling in androgenetic alopecia.

BACKGROUND: Wnt and transforming growth factor-ß (TGF-ß) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-ß signaling is altered in patients with AGA and whether there exists a crosstalk between them in pathogenetic process of AGA remain unclear. OBJECTIVES: To investigate the expression of Wnt and TGF-ß signaling and the crosstalk between these 2 signaling pathways in AGA. METHODS: Fifteen male patients with AGA were recruited for our research. Fifteen scalp specimens of the balding were collected from frontal areas, and 9 nonbalding were collected from occipital areas. We analyzed the expression and activation of downstream Wnt and TGF-ß signaling molecules in both balding and nonbalding hair follicles isolated from scalp specimens. Furthermore, we evaluated the activation of Wnt and TGF-ß signaling after either of them was blocked with the inhibitor in balding and nonbalding dermal papilla (DP) cells. RESULTS: Compared with the nonbalding counterparts, the mRNA level of Wnt10a and LEF1 was decreased. But TßRI and TßRII, and the protein expression of TGF-ß1 was elevated in balding hair follicles. To investigate the crosstalk between Wnt and TGF-ß signaling, we used SB431542 to inhibit the TGF-ß signaling in balding DP cells and found that SB431542 significantly attenuated the phosphorylation of Smad2 and Akt. However, the mRNA level of Wnt10a, LEF1, and the nuclear translocation of ß-catenin was increased. On the other hand, we suppressed the Wnt signaling by XAV939 in nonbalding DP cells, which displayed that the level of ß-catenin and LEF1 was significantly inhibited; however, the level of active TGF-ß1 and the phosphorylation of Smad2 and Akt were up-regulated. CONCLUSIONS: These data indicate that crosstalk between Wnt/ß-catenin and TGF-ß signaling pathways may exist as one of the important mechanisms contributing to AGA.

Quality of life in women with female pattern hair loss and the impact of topical minoxidil treatment on quality of life in these patients.

Female pattern hair loss (FPHL) is the most common hair loss disorder in women and it may impact on the psychological and social activities of patients, thereby reducing their quality of life (QoL). Topical minoxidil has been shown to be effective and safe in the treatment of patients with FPHL. The aim of this study was to assess the QoL of patients with FPHL and investigate whether topical minoxidil solution treatment improves the QoL of these patients. In this study, we enrolled 125 female patients aged 16-72 years to answer visual analog scale (VAS) and dermatology life quality index (DLQI) questionnaires. Of these patients, 31 were recruited for the follow-up study after 12 months of treatment with 2% minoxidil. Each index and the change in QoL prior to and following treatment were statistically analyzed. There was identified to be a correlation between clinical severity and the values of the indices in all patients. There was a statistically significant difference between the VAS and DLQI scores prior to and following treatment with 2% minoxidil. A comparison between the good responders (n=23) and the poor responders (n=8) revealed no significant difference in the improvement of VAS and DLQI scores. The QoL of the patients was severely impaired by FPHL. The DLQI and VAS used in this study were validated as useful indices for the evaluation of QoL due to their high reliability, sensitivity and simplicity. This evaluation is recommended for the management of FPHL treatment. The results of the study demonstrated that topical minoxidil improved the QoL of the patients.

[Effect of tacrolimus on the growth cycle of murine hair follicles].

OBJECTIVE: To explore the effect of tacrolimus on murine hair follicle cycle. METHOD: Hematoxylin-eosin dyeing and reverse transcription-polymerase chain raction techniques were used. RESULTS: Five days after depilation, the hair follicles in both the tacrolimus group and the minoxidil group was in anagen V, while that in the vaseline group was in anagen III. vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) were detected in back skin in both the tacrolimus group and the minoxidil group, but not in the vaseline group. CONCLUSION: Tacrolimus can promote the growth of hair by stimulating the hair follicle to enter anagen V in mice, which may be explained by the effects of VEGF and HGF.

[Effect of hypoxia inducible factor-1alpha on cells of hair follicle].

OBJECTIVE: To investigate the feasibility of stable transfection of human hypoxia inducible factor-1alpha (HIF-1alpha) gene into fibroblasts cells and the effects of supernatant from the transfected cell culture on hair follicle cells. METHODS: PcDNA-HIF1alpha was stably transfected into fibroblasts cells with lipofectamine 2000. Expression of HIF-1alpha was observed by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The supernatant was obtained to detect the expression of vascular endothelial growth factor (VEGF) by ELISA. The mRNA expression of basic fibroblast growth factor (bFGF) was detected by RT-PCR. MTT was used to detect the activity of fibroblasts cells and dermal sheath cells added with supernatant. RESULTS: PcDNA-HIF1alpha was successfully transfected into fibroblasts cells. HIF-1alpha could be detected by RT-PCR and Western blot. The expression of VEGF in the supernatant of cells transfected with PcDNA-HIF1alpha was detected. The mRNA expression of bFGF was significantly higher than in the control group (P < 0.01). MTT showed the activity of cells added with supernatant was enhanced (P < 0.05). CONCLUSION: PcDNA-HIF1alpha can stably transfected into fibroblasts cells, and the expressed HIF-1alpha induces the expression of VEGF and bFGF, and the expressed VEGF enhances the activity of cells.