Prostaglandin D2-Mediated DP2 and AKT Signal Regulate the Activation of Androgen Receptors in Human Dermal Papilla Cells
Open accessAbstract
Prostaglandin D2 (PGD2) and prostaglandin D2 receptor 2 (DP2) is known to be an important factor in androgenetic alopecia (AGA). 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 AGA involving PGD2-DP2 in hDPCs.
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Other prostaglandin synthases in the same family as PTGES3 have been implicated in the production of androgens.
“other prostaglandin synthases in the same family as PTGES3 have been implicated in the production of androgens48,49.”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [49]
The Introduction identifies PTGDS as a prostaglandin synthase, and the Conclusions link its product, PGD2, to androgen-receptor activity in human dermal papilla cells. Neither passage says PTGDS produces androgens; the Introduction instead says androgens can stimulate PTGDS. The copy also does not establish PTGDS’s family relationship to PTGES3. (LLM, conf=0.85)
Experimental — accuracy not yet measuredPTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus.
“PTGES3 protein is reported to have several protein functions and to be localized to both the cytosol and nucleus41–49 (Fig. 3f).”
From Genome-scale CRISPR screens identify PTGES3 as a direct modulator of androgen receptor function in advanced prostate cancer (2025) · cites this paper as [49]
The Introduction and Discussion address PTGDS, PGD2, and androgen-receptor signaling, but do not address PTGES3 protein functions or its cellular localization. Searches for PTGES3, cytosol/nucleus localization, and prostaglandin E synthase 3 found no relevant passage in our copy; page numbers were unavailable. (LLM, conf=0.76)
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- Authors
- Jeong, K., Jung, J., Kim, J., & Kang, H.
- Affiliations
- St. Paul's Hospital (KR)
- Corresponding author
- Kang, Hoon
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2018-02-12
- Volume
- 19
- Issue
- 2
- Pages
- 556
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC5855778
- OpenAlex
- W2791100636
- Cited by
- 30
- References
- 37
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 4 · 2022: 7 · 2021: 5 · 2019: 4 · 2018: 1
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- This research was supported by the Ministry of Trade, Industry & Energy (MOTIE), Korea Institute for Advancement of Technology (KIAT) through the Encouragement Program for The Industries of Economic Cooperation Region (R0005754)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
- Keywords
- prostaglandin D2, DP2 receptor, Akt signaling, androgen receptor, dermal papilla cells, androgenetic alopecia, hair follicle, TGF-β1, CREB, GSK3β, insulin-like growth factor I, LY294002
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Cells, Cultured, Female, Humans, Insulin-Like Growth Factor I, Middle Aged, Receptors, Androgen, Receptors, Immunologic, Receptors, Prostaglandin, Prostaglandin D2, Signal Transduction, Cyclic AMP Response Element-Binding Protein, Hair Follicle, Dermis, Proto-Oncogene Proteins c-akt, Lymphoid Enhancer-Binding Factor 1, Transforming Growth Factor beta1
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