Hypoxic conditions induce the activation of hypoxia-inducible factor-1α (HIF-1α) to restore the supply of oxygen to tissues and cells. Activated HIF-1α translocates into the nucleus and binds to hypoxia response elements to promote the transcription of target genes. Cathepsin L (CTSL) is a lysosomal protease that degrades cellular proteins via the endolysosomal pathway. In this study, we attempted to determine if CTSL is a hypoxia responsive target gene of HIF-1α, and decipher its role in melanocytes in association with the autophagic pathway. The results of our luciferase reporter assay showed that the expression of CTSL is transcriptionally activated through the binding of HIF1-α at its promoter. Under autophagy-inducing starvation conditions, HIF-1α and CTSL expression is highly upregulated in melan-a cells. The mature form of CTSL is closely involved in melanosome degradation through lysosomal activity upon autophagosome–lysosome fusion. The inhibition of conversion of pro-CTSL to mature CTSL leads to the accumulation of gp100 and tyrosinase in addition to microtubule-associated protein 1 light chain 3 (LC3) II, due to decreased lysosomal activity in the autophagic pathway. In conclusion, we have identified that CTSL, a novel target of HIF-1α, participates in melanosome degradation in melanocytes through lysosomal activity during autophagosome–lysosome fusion.

The International Society for Cutaneous Lymphoma (ISCL) proposes a diagnostic algorithm for early mycosis fungoides (MF) that includes clinical, histological, immunophenotypical, and molecular criteria. Here, we analyzed the immunologic markers and features of T-cell clonality in 38 early MF cases and 22 non-MF cases to validate the ISCL algorithm. We found that CD5 and CD7 expression differed significantly between early MF and non-MF cases, with epidermal discordance of CD7 expression more frequently identified in early MF. Notably, increasing the cut-off value for CD7 expression from 10% to 22.5% improved its sensitivity. Furthermore, TCR-γ and β chain rearrangements were more frequently detected in early MF than in non-MF cases. Based on these findings, we propose CD5 and CD7 deficiency as mandatory immunopathologic criteria and PCR-based testing for TCR-γ and β chains as required molecular/biologic criteria to improve the efficiency of early MF diagnosis using the ISCL algorithm.

Androgenetic alopecia (AGA) is the most common type of hair loss and affects both men and women. Male pattern hair loss shows characteristic frontal recession and vertex baldness, whereas female pattern hair loss produces diffuse alopecia over the mid-frontal scalp. AGA is mediated by increased androgen susceptibility in affected scalp hairs. 5α-Reductase converts testosterone into dihydrotestosterone, a potent androgen, in the scalp. Both androgen receptors and 5α-reductase have higher expression levels in the balding scalp than in non-affected regions. Increased androgen susceptibility induces hair follicle miniaturization, which leads to the progressive loss of thicker terminal hairs in the balding scalp. Currently, topical minoxidil and oral 5α-reductase inhibitors, such as finasteride and dutasteride, are approved options for the pharmacological treatment of AGA. Topical minoxidil remains the mainstay of therapy for mild to moderate AGA in both men and women. The daily intake of 1-mg finasteride or 0.5-mg dutasteride shows better efficacy than topical minoxidil in regard to hair regrowth in male AGA. Anti-androgens can be used in female AGA wit clinical and biochemical evidence of hyperandrogenism. Patients may be overwhelmed and confused by the variety of treatment options for AGA management, including over-the-count drugs with low evidence quality. Therefore, physicians must be aware of the current guidelines for the management of AGA based on evidence-based approaches to select better options for patients.