Background:Wnt and transforming growth factor-β (TGF-β) signaling pathways are known to be involved in the pathogenesis of androgenetic alopecia (AGA). However, the way that Wnt and TGF-β 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-β 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-β signaling molecules in both balding and nonbalding hair follicles isolated from scalp specimens. Furthermore, we evaluated the activation of Wnt and TGF-β 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 TβRI and TβRII, and the protein expression of TGF-β1 was elevated in balding hair follicles. To investigate the crosstalk between Wnt and TGF-β signaling, we used SB431542 to inhibit the TGF-β 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 β-catenin was increased. On the other hand, we suppressed the Wnt signaling by XAV939 in nonbalding DP cells, which displayed that the level of β-catenin and LEF1 was significantly inhibited; however, the level of active TGF-β1 and the phosphorylation of Smad2 and Akt were up-regulated.Conclusions:These data indicate that crosstalk between Wnt/β-catenin and TGF-β signaling pathways may exist as one of the important mechanisms contributing to AGA.

The use of confocal laser scanning microscopy (CLSM) may be an eligible alternative for confirmation of the diagnosis of hypopigmented macules. Our purpose was to evaluate CLSM features for non-invasive imaging of vitiligo, nevus depigmentosus and postinflammatory hypopigmentation in vivo. A total of 68 patients with a clinical diagnosis of the aforementioned diseases were included in this study. CLSM was performed on lesional and adjacent normal appearing skin for all patients. In the active and stable phases of vitiligo, CLSM demonstrated a complete loss of melanin in lesional skin in 14 of 25 patients (56.0%) and 16 of 20 patients (80.0%), respectively. In 11 of 25 (44.0%) patients, the amount of melanin in lesional skin decreased in the active phase of vitiligo, but it is noteworthy to know that the melanin was distributed homogeneously in the dermal papillary rings. In four of 20 patients (20.0%), the dermal papillary rings disappeared completely, but some refractile granules and dendrites could be seen in the stable phase of vitiligo, which may indicate the start of vitiligo repigmentation. Although, in 20 of 20 patients (100%) with nevus depigmentosus, the dermal papillary rings lost their integrity and the content of melanin decreased obviously, there must have been melanin in the dermal papillary rings during its development in all patients. Simultaneously, the melanin was distributed heterogeneously in the dermal papillary rings. The content of melanin and dermal papillary rings in postinflammatory hypopigmentation probably depend on the depth and site of the inflammation; moreover, melanophages were observed in postinflammatory hypopigmentation but did not exist in vitiligo and nevus depigmentosus. In addition, the content of melanin and dermal papillary rings in adjacent normal appearing skin showed changes in the active phase of vitiligo but showed no changes in any of the patients in the stable phases of vitiligo, nevus depigmentosus and postinflammatory hypopigmentation. Differences based on CLSM in the aforementioned diseases were the content of melanin and its distribution pattern. CLSM may be useful to discriminate vitiligo, postinflammatory hypopigmentation and nevus depigmentosus in a non-invasive fashion.

Proteins involved in repression of the human beta-globin gene may be useful in the treatment of sickle cell anemia, in conjunction with therapy to reactivate fetal globin genes. If there is a reciprocal elevation of gamma-globin expression upon repression, this approach could be useful in additional hemoglobinopathies. We previously showed that repression of the beta-globin gene appears to be mediated through two DNA sequences, silencers I and II, and identified a protein termed BP1 which binds to both silencer sequences. In this study, we cloned two cDNAs encoding proteins which bind to an oligonucleotide in silencer I containing a BP1 binding site. These cDNAs correspond to HMG-I and HMG-Y, isoforms regarded as architectural proteins. We demonstrate that binding of HMG-I(Y) to this oligonucleotide causes bending/flexure of the DNA. HMG-I(Y) also binds to a second oligonucleotide containing a BP1 binding site located in a negative control region upstream of the delta-globin gene, suggesting a role for HMG-I(Y) in repression of adult globin genes. Expression studies revealed that HMG-I(Y) is ubiquitously expressed in human tissues that do not express beta-globin, being present in 48 of 50 tissues and six hematopoietic cell lines examined. Furthermore, HMG-I(Y) expression is down-regulated during differentiation of primary erythroid cells. We present a model in which HMG-I(Y) alters DNA conformation to allow binding of repressor proteins, and in which the relative amount of HMG-I(Y) helps to determine the repressive state of the beta-globin gene.

By understanding the CLSM features of honeycomb pattern, cobblestone pattern, ringed pattern and dermal papillae individually or in combination, the findings support the roles of these characteristic architectures in diagnosis and differential diagnosis of skin diseases.