일차 섬모(primary cilia)는 세포에서 안테나처럼 돌출되어 나온 기관인데, 외부 자극에 반응할 수 있는 각종 수용체와 채널, 신호 전달 인자들을 가지고 있다. 피부는 자외선, 온도, 습도, 중력, 장력 등 외부 환경에 반응하여 멜라닌이나 콜라겐을 만들고 피부 장벽을 형성한다. 피부에서는 일차 섬모가 없으면 헤어의 생성이나 각질의 분화가 억제된다는 보고가 있다. 또한 피부 색소 생성과 관련하여서는 일차 섬모가 sonic hedgehog-smoothened-GLI2 신호 전달에 의해 활성화되면 멜라닌 생성이 억제된다는 것이 알려져 있다. 피부가 자외선을 받으면 멜라닌 생성 호르몬의 양이 증가하고 멜라닌 생성 호르몬은 멜라닌 생성 세포 내 cAMP의 양을 증가시켜 멜라닌 생성 효소의 발현을 높인다. 이에 멜라닌 생성 호르몬과 세포 내 cAMP의 양을 증가시키는 물질을 처리하여 멜라닌 생성을 높였을 때 일차 섬모의 변화를 확인한 결과 일차 섬모가 감소하는 것을 확인하였다. 또한 기존 미백 원료인 유용성 감초 추출물(an ethanol extract of Glycyrrhiza glabra (EGG) root)과 Melasolv (3,4,5-trimethoxy cinnamate thymol ester (TCTE))가 일차 섬모의 발현을 증가시키고 멜라닌 생성 효소인 tyrosinase의 발현을 억제함을 확인할 수 있었다. 따라서 일차 섬모를 조절할 수 있다면 피부 색소 침착을 효과적으로 조절할 수 있을 것이다.
일차 섬모(primary cilia)는 세포에서 안테나처럼 돌출되어 나온 기관인데, 외부 자극에 반응할 수 있는 각종 수용체와 채널, 신호 전달 인자들을 가지고 있다. 피부는 자외선, 온도, 습도, 중력, 장력 등 외부 환경에 반응하여 멜라닌이나 콜라겐을 만들고 피부 장벽을 형성한다. 피부에서는 일차 섬모가 없으면 헤어의 생성이나 각질의 분화가 억제된다는 보고가 있다. 또한 피부 색소 생성과 관련하여서는 일차 섬모가 sonic hedgehog-smoothened-GLI2 신호 전달에 의해 활성화되면 멜라닌 생성이 억제된다는 것이 알려져 있다. 피부가 자외선을 받으면 멜라닌 생성 호르몬의 양이 증가하고 멜라닌 생성 호르몬은 멜라닌 생성 세포 내 cAMP의 양을 증가시켜 멜라닌 생성 효소의 발현을 높인다. 이에 멜라닌 생성 호르몬과 세포 내 cAMP의 양을 증가시키는 물질을 처리하여 멜라닌 생성을 높였을 때 일차 섬모의 변화를 확인한 결과 일차 섬모가 감소하는 것을 확인하였다. 또한 기존 미백 원료인 유용성 감초 추출물(an ethanol extract of Glycyrrhiza glabra (EGG) root)과 Melasolv (3,4,5-trimethoxy cinnamate thymol ester (TCTE))가 일차 섬모의 발현을 증가시키고 멜라닌 생성 효소인 tyrosinase의 발현을 억제함을 확인할 수 있었다. 따라서 일차 섬모를 조절할 수 있다면 피부 색소 침착을 효과적으로 조절할 수 있을 것이다.
The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Sk...
The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Skin responds to external stimuli and differentiates by making melanin, collagen and horny layer. Ciliogenesis participates in developmental processes of skin, such as keratinocyte differentiation and hair formation. And it was reported that skin pigmentation was inhibited when ciliogenesis was induced by sonic hedgehog-smoothened-GLI2 signaling. When skin is exposed to ultraviolet irradiation, alpha-melanocyte stimulating hormones (${\alpha}$-MSH) increase melanin synthesis through activation of the cAMP pathway in melanocytes. We observed that ${\alpha}$-MSH and cAMP production inducers inhibited ciliogenesis of melanocytes. Therefore, we thought that regulation of ciliogenesis is potential candidate target for the development of agents to treat undesirable hyperpigmentation of skin. As a result, we found out that an ethanol extract of Glycyrrhiza glabra (EGG) root and 3,4,5-trimethoxy cinnamate thymol ester (TCTE, Melasolv) significantly inhibit melanin synthesis of normal human melanocyte by inducing primary cilium formation. This study proposed new theory to regulate skin pigmentation and cosmetic components for skin whitening.
The primary cilium protrudes from the cell body like a bio-antenna that has many receptors, channels and signaling molecules to sense and response to external stimuli. The external environment such as ultraviolet irradiation, temperature, humidity, gravity and shear stress always influences skin. Skin responds to external stimuli and differentiates by making melanin, collagen and horny layer. Ciliogenesis participates in developmental processes of skin, such as keratinocyte differentiation and hair formation. And it was reported that skin pigmentation was inhibited when ciliogenesis was induced by sonic hedgehog-smoothened-GLI2 signaling. When skin is exposed to ultraviolet irradiation, alpha-melanocyte stimulating hormones (${\alpha}$-MSH) increase melanin synthesis through activation of the cAMP pathway in melanocytes. We observed that ${\alpha}$-MSH and cAMP production inducers inhibited ciliogenesis of melanocytes. Therefore, we thought that regulation of ciliogenesis is potential candidate target for the development of agents to treat undesirable hyperpigmentation of skin. As a result, we found out that an ethanol extract of Glycyrrhiza glabra (EGG) root and 3,4,5-trimethoxy cinnamate thymol ester (TCTE, Melasolv) significantly inhibit melanin synthesis of normal human melanocyte by inducing primary cilium formation. This study proposed new theory to regulate skin pigmentation and cosmetic components for skin whitening.
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가설 설정
Primary cilia are involved in keratinocyte differentiation, hair follicle maturation and pigmentation in skin induced by UV radiation. In this report, we tested the effects of skin whitening components on ciliogenesis. EGG and TCTE inhibited melanogenesis effectively by inducing primary cilium formation.
제안 방법
NHEMs were treated with TCTE (10 ppm), EGG (1 ppm) and ciliobrevin A1 (Cilio A, 5 µM) for 4 days.
NHEMs were treated with cytochalasin D (Cyto D, 0.25 mM), TCTE (10 ppm), EGG (1 ppm) and ciliobrevin A1 (Cilio A, 5 µM) for 4 days.
대상 데이터
05% [v/v] Tween®20), the membranes were incubated overnight with specific primary antibodies. Anti-polyglutamylated-tubulin antibody (AG-20B-0020, 1:1000) was purchased from Adipogene (San Diego, CA);anti-tyrosinase antibody (05-647; 1 : 1000) was purchased from Upstate Biotechnology (Lake Placid, NY, USA);anti-TRP1 antibody and anti-GAPDH antibody (sc25778; 1 : 2000) were obtained from Santa Cruz Biotechnology (Dallas, Texas, USA). For protein detection, the membranes were incubated with HRP-conjugated secondary antibodies and the signals were detected with SuperSignal West Dura HRP Detection Kit (Pierce, Rockford, IL).
데이터처리
Data were obtained from at least 3 independent experiments and are presented as mean ± S.E. Statistical evaluation of the results was performed using 1-way ANOVA (SPSS software, version 21).
성능/효과
It was attributed to low concentration because we observed inhibitory effect of EGG on protein expression of tyrosinase at high concentration (data not shown). Consequently, these data demonstrated that EGG and TCTE inhibited melanogenesis of NHEMs by increasing primary cilium formation.
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