Story Of P1P :: '스트레스탈모' 태그의 글 목록

Induction of hair growth by phytosphingosine-1-phosphate (P1P) in C3H/HeJ mice model

P1P (0.01%)를 피부에 도포하면 모발성장이 촉진되는 것을 발표하였으며, Minoxidil과 유사한 정도로 hair growth가 일어나며, minoxidil angen (성장기)에서 catagen (퇴행기)으로 많이 진행되며, P1P telogen (휴지기)에서 anagen (성장기)으로 전환되는 양상을 보이며, P1P hair growth 기전으로 B-Catenin  Wnt 단백질의 발현을 증가시킴따라서 P-1-P는 탈모치료에 유용하게 사용할 수 있는 물질임.

2012, 유럽피부모발학회 발표 -PMK-


Molecular principles of hair follicle induction and morphogenesis

모낭 형성에 중용한 역할을 하는 단백질은 B-Catenin Wnt 단백질임. Wnt 단백질은 모발의 발생과 성장에 관여하는 신호전달 단백질임. Wnt 신호전달이 없으면 epidermal cell fate로 가지만, Wnt 신호전달이 활성화되면 hair follicle fate로 감. Wnt에 의한 신호전달이 B-Catenin으로 이어져 모낭형성이 이루어짐. 따라서 B-Catenin Wnt 단백질의 형성이 탈모치료에 중요한 역할을 담당함.

Our present working hypothesis, for induction of primary (guard; A) and secondary (non-guard, awl; B and C) pelage hair follicles. A: On the left side, the different stages of early hair follicle development are depicted (stage 0–5), according to the original hypothesis of M. Hardy.(6) In mammals, it is not yet known how inductive fields are created prior to initiation of hair follicle placode formation. Thus, the question mark above stage 0. To the right the currently known activation pathways involved in primary guard hair development are shown. Essential inducers are Wnt and EdaA1/EdaR/NF-kB. B: Secondary hair induction calls for Wnt and Noggin. A model concerning inhibition of BMP4 in the dermal papilla and BMP2 in the ectoderm by BMP anatgonist Noggin was proposed by Botchkarev et al.(24) Localized Noggin expression in the dermal papilla antagonizes the potent placode-growth-inhibitory action of the two BMPs and leads to Lef-1 expression. Noggin also inhibits p75NTR expression, which functions as a receptor that negatively regulates hair follicle growth.(94) Jamora et al. go a step further in proposing that Noggin is directly responsible for activation of uclear Lef-1 expression in secondary hair follicles.(33) They suggest that Noggin must counteract any BMP action in the developing follicle because BMP is the key inhibitor of Lef-1 expression. Figure adapted from Botchkarev et al.(24) C: Scheme of the currently known signaling pathways involved in secondary awl hair induction. As shown in B, apart from Wnt signaling, Noggin is the second essential inducer. The numbers (1.–3.) indicate the possible order of events occuring to initiate awl hair development. One major difference of primary guard hairs compared to secondary awl hairs is the EdaA1/EdaR/NF-kB pathway, only activated during initiation of guard hairs. Inhibition of any component of this pathway leads to absence of guard hairs.(22,23) Wnt in both pathways stands for any Wnt, the exact one being unknown. The best-defined so-alled ‘‘inhibitors’’ of hair follicle development, Dkk1 and BMPs, are boxed and marked in black. Dkk1 is a true inhibitor and, ectopically expressed in the ectoderm,it prevents formation of all hair follicle types by complete inhibition of Wnt signaling.(30) However, BMPs do not have a clear inhibitory role. They are in part activators and inhibitors, depending on the developmental stage. BMPs are expressed from early on in both hair types, and at least in secondaryHFstheyseemto be needed for active b-catenin complexes and downstream target gene expression of Wnt/b-catenin/Lef-1.(110,111) The exact role of BMPs in early guard hair follicles remains unknown. However, BMP action may have to be anatgonized by Noggin at later stages of guard hair follicle morphogenesis.(25,112) Shh/Gli2 signaling is activated at a later time point at stage 2–3(hair germ—peg), and is only to a minor degree responsible for dermal papilla formation of both hair types, but seems to be required for dermal Wnt5a expression.(29) Shh/Gli2 is mostly essential for further epidermal downgrowth of the germ and the subsequent peg formation.(12) The formation of secondary zigzag hairs remains to be studied in detail. They seem to demand EdaA1/EdaR/NF-kB signaling later than in guard hairs and further downstream of Wnt/b-catenin and Noggin/Lef-1. Importantly, note that the arrows do not necessarily mean that the protein is directly regulated by a particular pathway, with the exception of Wnt/b-catenin, Eda/NF-kB and Shh/Gli2. In most cases, it means that the indicated protein is activated temporarily downstream. The multiple question marks already imply that there are still many processes that are currently unknown and need to be investigated in the future.

2005, BioEssays



B-Catenin controls hair follicle morphogenesis and stem cell differentiation in the skin


B-Catenin Wnt/wingless 신호전달에 중요한 단백질이며, 배아발생에서 결정적인 단계를 조절하는 단백질임. 또한 모낭의 형성에 중요한 역할을 하는 단백질임. B-Catenin에 돌연변이가

일어나면, 배아발생에서 모낭형성이 억제됨. 모낭이 형성된 후에 B-Catenin이 제거되면, 첫 번째 hair cycle 후에 hair가 완전히 없어짐. 또한 B-Catenin은 모낭 속에 있는 (벌지에 있는) 줄기세포의 운명을 결정하는 단백질임. B-Catenin이 존재하면 줄기세포가 모모세포로 분화가 되지만, B-Catenin이 없으면 줄기세포가 모모세포가 되지 못하고 피부세포로 분화가 됨. 따라서 B-Catenin은 줄기세포가 모모세포로 분화하는 운명을 결정하는 단백질임. 따라서 B-Catenin 단백질의 양을 증가시키는 물질을 탈모치료에 유용하게 사용됨.

Scheme of the Possible Roles of b-Catenin in Hair Follicle Morphogenesis and Skin Stem Cell Differentiation

(a) The genetic placement of b-catenin in the ordered interplay of various signaling pathways mediated by FGF, Downless, BMP, and SHH is shown.

(b) The putative role of b-catenin in the fate decision of stem cells of the bulge between the follicular or epidermal keratinocyte lineages is shown. Modified from Fuchs and Segre, 2000 and Taylor et al., 2000.

2001, Cell


cell 105 533 545 2001.pdf

CRF receptor antagonist Astressin-B reverses and [revents alopecia in CRF over-expressing mice


Corticotrophin-releasing factor (CRF) 신호전달 경로는 스트레스 반응에 관여하며, 스트레스에 노출되면 모낭에서 hair growth의 억제가 일어나는 증거들이 많이 있음. Corticotrophin은 스트레스에 의해 분비되는 호르몬임. CRF receptor를 차단하는 물질 (스트레스 억제 물질) hair growth에 어떤 영향을 주는지 조사하였다. Astressin B CRF1 CRF2를 차단하는 물질 (스트레스 억제물질)로 피하주사나 복강주사를 할 경우 탈모를 회복시킨다고 보고함. 또한 이 물질을 피하주사하면 탈모로 발달하지 않도록 예방하는 작용도 함.

Figure 1. The CRF1/CRF2 receptor antagonist, astressin-B, injected intraperitoneally (ip) in CRF-OE mice with fully developed alopecia induces hair growth and pigmentation. Photographs: Row A: Male CRF-OE mice (4 months old) injected ip once daily for 5 consecutive days with saline at 3 days after the last injection and Row B: astressin-B (5 mg/mouse) at 3 days after the last ip injection, and Row C: the

same mice as in the middle panel Row B at 4 weeks after the last ip injection.


2011, PlosOne



Substance P as an immunomodulatory neuropeptide in a mouse model for autoimmune hair loss (Alopecia Areata)

Alopecia areata (원형탈모) hair follicle의 자가면역질환으로 substance P가 중요한 역할을 수행함. 원형탈모의 초기상태에서 substance P에 반응하는 신경섬유의 수가 증가하고, 원형탈모가 진행된 경우에는 substance P에 반응하는 신경섬유가 감소하며, substance P를 분해하는 효소 (neutral endopeptidase)가 증가한다. Substance P hair follicle regression을 촉진하고, 비만세포의 탈 과립을 촉진하여 염증반응을 야기함. Substance P를 피부에 도포할 경우 비만세포의 탈과립이 증가하고 hair follicle regression을 촉진함. 이외에 활성화된 CD8+ Tcell을 증가시켜 면역세포가 모낭을 공격하게 함. 스트레스는 substance P를 생성하게하고, 이 물질이 원형탈모를 유도하는 좋은 증거가 됨.

2007, Jouranal Investigative Dermatology


SP-autoimmune hair loss.pdf

Probing the effects of stress mediators on the human hair follicle : Substance P holds central position

스트레스는 hair growth를 변경시키는데, substance P nerve growth factor (NGF)가 중요한 역할을 수행함. Substance P는 스트레스에 연관된 neuropeptide (신경전달 펩티드)로 이 논문에서는 substance P가 모발성장에 어떤 영향을 미치는지 조사함. Substance P hair shaft elongation을 억제하고, 미성숙 catagen 발달을 촉진함. Substance P는 비만세포 (mast cell)의 탈 과립을 촉진하여 염증반응을 촉진하고, NGF 생성 촉진과 세포사멸을 유도함. 따라서 스트레스는 substance P를 만들어, 세포성장을 억제하고, 염증반을을 야기하며, 세포사멸을 촉진해 모발성장를 억제함. 스트레스가 탈모의 원인임을 밝히고 있음.

스트레스에 의해 세포가 사멸되는 것을 억제하기 위해 혈소판에서는 S1P(P1P)를 분비 함.

 2007, American Journal Pathology


stress-human follicle.pdf


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