Extract of Scutellaria baicalensis induces semaphorin 3A production in human epidermal keratinocytes

In a disease-state-dependent manner, the histamine-resistant itch in dry skin-based skin diseases such as atopic dermatitis (AD) and xerosis is mainly due to hyperinnervation in the epidermis. Semaphorin 3A (Sema3A) is a nerve repulsion factor expressed in keratinocytes and it suppresses nerve fiber elongation in the epidermis. Our previous studies have shown that Sema3A ointment inhibits epidermal hyperinnervation and scratching behavior and improves dermatitis scores in AD model mice. Therefore, we consider Sema3A as a key therapeutic target for improving histamine-resistant itch in AD and xerosis. This study was designed to screen a library of herbal plant extracts to discover compounds with potential to induce Sema3A in normal human epidermal keratinocytes (NHEKs) using a reporter gene assay, so that positive samples were found. Among the positive samples, only the extract of S. baicalensis was found to consistently increase Sema3A levels in cultured NHEKs in assays using quantitative real-time PCR and ELISA. In evaluation of reconstituted human epidermis models, the level of Sema3A protein in culture supernatants significantly increased by application of the extract of S. baicalensis. In addition, we investigated which components in the extract of S. baicalensis contributed to Sema3A induction and found that baicalin and baicalein markedly increased the relative luciferase activity, and that baicalein had higher induction activity than baicalin. Thus, these findings suggest that S. baicalensis extract and its compounds, baicalin and baicalein, may be promising candidates for improving histamine-resistant itch via the induction of Sema3A expression in epidermal keratinocytes.

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Retinoid-related orphan receptor α is involved in induction of semaphorin 3A expression in normal human epidermal keratinocytes

Journal of Dermatological Science ◽

10.1016/j.jdermsci.2015.03.015 ◽

2015 ◽

Vol 79 (1) ◽

pp. 84-86 ◽

Cited By ~ 5

Author(s):

Yayoi Kamata ◽

Mitsutoshi Tominaga ◽

Azumi Sakaguchi ◽

Yoshie Umehara ◽

Osamu Negi ◽

...

Keyword(s):

Orphan Receptor ◽

Epidermal Keratinocytes ◽

Semaphorin 3A ◽

Human Epidermal Keratinocytes ◽

Normal Human Epidermal Keratinocytes ◽

Normal Human

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miR-136 Modulates TGF-β1-Induced Proliferation Arrest by Targeting PPP2R2A in Keratinocytes

BioMed Research International ◽

10.1155/2015/453518 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 7

Author(s):

Dianbao Zhang ◽

Jing Wang ◽

Zhe Wang ◽

Tao Zhang ◽

Ping Shi ◽

...

Keyword(s):

Molecular Mechanisms ◽

Skin Wound ◽

Luciferase Reporter ◽

Epidermal Keratinocytes ◽

Dependent Manner ◽

Hacat Cells ◽

Skin Wound Healing ◽

Human Epidermal Keratinocytes ◽

Reporter Assays ◽

Normal Human

Keratinocytes proliferation is critical for the capacity to heal wounds and accumulating evidences have proved that dysregulation of microRNAs is involved in proliferation of keratinocytes. However, the molecular mechanisms remain to be completely elucidated. Here, we show that miR-136 was significantly decreased by TGF-β1 treatment in HaCaT cells and normal human epidermal keratinocytes (NHEK), and it was a Smad3-dependent manner. By cell proliferation assay and cell cycle analysis, we found that reintroduction of miR-136 by transfection, as well as PPP2R2A silencing, counteracted TGF-β-induced proliferation arrest in HaCaT cells. Further, PPP2R2A was verified as a direct target of miR-136 by dual-luciferase reporter assays and Western blotting. These data suggest that miR-136 may play an important role during TGF-β1-induced proliferation arrest by targeting PPP2R2A in keratinocytes, which might represent a potential target for improving skin wound healing.

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