Prostaglandin D2-mediated Dp2 And Akt Signal Regulate The Activation Of Androgen Receptors In Human

[alscarmuzza]

Prostaglandin D2-Mediated DP2 and AKT Signal Regulate the Activation of Androgen Receptors in Human Dermal Papilla Cells.
Authors:
Jeong KH; Department of Dermatology, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul 02259, Korea. kwanho16@nate.com.
Jung JH; Department of Dermatology, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul 02259, Korea. kpajjh@naver.com.
Kim JE; Department of Dermatology, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul 02259, Korea. mdkjeun@naver.com.
Kang H; Department of Dermatology, St. Paul's Hospital, College of Medicine, The Catholic University of Korea, Seoul 02259, Korea. johnkang@catholic.ac.kr.
Source:
International Journal Of Molecular Sciences [Int J Mol Sci] 2018 Feb 12; Vol. 19 (2). Date of Electronic Publication: 2018 Feb 12.
Publication Type:
Journal Article
Language:
English
Journal Info:
Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: In Process
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
Abstract:
Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2) is known to be an important factor in androgenetic alopecia (Androgenetic Alopecia). However, the effect of PGD2 in human dermal papilla cells (hDPCs) is not fully understood. The function of PGD2-induced expression of the androgen receptor (AR), DP2, and AKT (protein kinase B) signal were examined by using real time-PCR (qRT-PCR), western blot analysis, immunocytochemistry (ICC), and siRNA transfection system. PGD2 stimulated AR expression and AKT signaling through DP2. PGD2 stimulated AR related factors (transforming growth factor beta 1 (TGFβ1), Creb, lymphoid enhancer binding factor 1 (LEF1), and insulin-like growth factor 1, (IGF-1)) and AKT signaling (GSK3β and Creb) on the AR expression in hDPCs. However, these factors were down-regulated by DP2 antagonist (TM30089) and AKT inhibitor (LY294002) as well as DP2 knockdown in hDPCs decreased AR expression and AKT signaling. Finally, we confirmed that PGD2 stimulates the expression of AR related target genes, and that AKT and its downstream substrates are involved in AR expression on hDPCs. Taken together, our data suggest that PGD2 promotes AR and AKT signal via DP2 in hDPCs, thus, PGD2 and DP2 signal plays a critical role in AR expression. These findings support the additional explanation for the development of Androgenetic Alopecia involving PGD2-DP2 in hDPCs.

Entry Date(s):
Latest Revision: 20180214
Update Code:
20180214
DOI:
10.3390/ijms19020556

 

[Trichosan]

Could we be witnessing an increase in research of Androgenetic Alopecia at the cellular and molecular level? Mighty good if so.

 

[whatevr]

Good. Now let's get a PGD2 inhibitor that does not cross the blood-brain barrier and f*** with people's sleep, and we're golden.

Fevipiprant?
Amira AM211?
Pulmagen ADC3680?

 

[Iah11]

our knowledge of human hair follicle biology seems to have expanded so much this decade,

 

[Jk1]

Good. Now let's get a PGD2 inhibitor that does not cross the blood-brain barrier and f*** with people's sleep, and we're golden.

Fevipiprant?
Amira AM211?
Pulmagen ADC3680?

cetrizine ?

 

[Armando Jose]

our knowledge of human hair follicle biology seems to have expanded so much this decade,

Yeah, but it is a pitty that they only studied a single case in the citated study,
:
Human Dermal Papilla Cell (hDPCs) Culture and Reagents
Human dermal papilla cells (hDPCs, sourced from scalp of a 57-old female

What happen in men, childrens, or body hair?

 

[whatevr]

cetrizine ?

H1 receptor antagonist. Nothing to do with this.

 

[Iah11]

Yeah, but it is a pitty that they only studied a single case in the citated study,
:
Human Dermal Papilla Cell (hDPCs) Culture and Reagents
Human dermal papilla cells (hDPCs, sourced from scalp of a 57-old female

What happen in men, childrens, or body hair?

Well women are susceptible to androgen related thinning as well but i wonder if that does mean that the study results have less utility.

Have you got any links for a clear, unifying hypothesis for Androgenetic Alopecia pathophysiology at a cellular level. Outside of any personal stake, hair follicle biology is so interesting.

So far, ive got this: That for some ill defined reason some men are susceptible to a cascade of events, when DHT binds the AR, that upregulates inflammatory pathways (eg CRTH) and apoptotic proteins. The excessive PGD2 mediates the chronic inflammation and causes a positive feedback mechanism, meaning theres always progressive element to Androgenetic Alopecia. At the same time, the binding of dht to the AR down regulates genes relating to normal hair follicle cycling and tissue regeneration (inhibition of JAK/STAT and wnt pathways e.g via upregulation of DKK1).

All this kind of suggests to me that finasteride really will always be a mainstay of Androgenetic Alopecia treatment just because its so far downstream. Any downstream treatment will miss out on treating some causes?

 

[InBeforeTheCure]

That's strange. Cotsarelis showed that DP2 wasn't expressed in the dermal papilla.

And also in an in vitro study, the DPCs didn't express DP2.

Outside of any personal stake, hair follicle biology is so interesting.

True dat.

 

[Armando Jose]

when DHT binds the AR, that upregulates inflammatory pathways (eg CRTH) and apoptotic proteins

Sebum alteration also can be inflammatory inducer.

"Current findings indicate that sebum lipid fractions with proinflammatory properties and inflammatory tissue cascades are associated in the process of the development of acne lesions. The oxidant/antioxidant ratio of the skin surface lipids and alterations of lipid composition are the main players in the induction of acne inflammation."
https://www.ncbi.nlm.nih.gov/pubmed/24134468

What do you think? All of us know that hair is always linked to sebaceous gland.... It is possible that hair fat can have a role in common baldness?

 

[Armando Jose]

Have you got any links for a clear, unifying hypothesis for Androgenetic Alopecia pathophysiology at a cellular level

I have not a study regarding this issue but common sense is a key and, have you any study demosytrating the different biology in scalp hair between men & women? I din´t find it.