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Keratinocyte Growth Inhibition through the
Modification of Wnt Signaling by Androgen in
Balding Dermal Papilla Cells
http://jcem.endojournals.org/content/94/4/1288.full.pdf
Keratinocyte Growth Inhibition through the
Modification of Wnt Signaling by Androgen in
Balding Dermal Papilla Cells
Tomoko Kitagawa, Ken-Ichi Matsuda, Shigeki Inui, Hideya Takenaka, Norito Katoh,
Satoshi Itami, Saburo Kishimoto, and Mitsuhiro Kawata
Departments of Dermatology (T.K., H.T., N.K., S.K.) and Anatomy and Neurobiology (T.K., K.-I.M., M.K.), Kyoto
Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-5586, Japan; and Department of
Regenerative Dermatology (S.In., S.It.), Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Context/Objective:
Androgen induces androgenetic alopecia (Androgenetic Alopecia), which has a regressive effect
on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to
positivelyaffectmammalianhairgrowth.Wehypothesizedthatandrogenreduceshairgrowthvia
an interaction with the Wnt signaling system. The objective of this study was to investigate the
effect of androgen on Wnt signaling in dermal papilla (DP) cells.
Design:
The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a
coculturesystemconsistingofDPcellsandkeratinocytes.Themolecularmechanismsofandrogenand
Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular local-
ization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules.
Results:
Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotest-
osterone in coculture with DP cells that were derived from Androgenetic Alopecia patients, but growth was not
suppressed in coculture with DP cells from non-Androgenetic Alopecia males. Whereas DP cells from both scalp
regions expressed AR protein, the expression levels of AR and cotranslocation with
-catenin, a
downstreamWntsignalingmolecule,werehigherinDPcellso***ApatientsthaninDPcellsfrom
non-Androgenetic Alopecia males. In addition, significant suppression of Wnt signal-mediated transcription in re-
sponse to dihydrotestosterone treatment was observed only in DP cells from Androgenetic Alopecia patients.
Modification of Wnt Signaling by Androgen in
Balding Dermal Papilla Cells
http://jcem.endojournals.org/content/94/4/1288.full.pdf
Keratinocyte Growth Inhibition through the
Modification of Wnt Signaling by Androgen in
Balding Dermal Papilla Cells
Tomoko Kitagawa, Ken-Ichi Matsuda, Shigeki Inui, Hideya Takenaka, Norito Katoh,
Satoshi Itami, Saburo Kishimoto, and Mitsuhiro Kawata
Departments of Dermatology (T.K., H.T., N.K., S.K.) and Anatomy and Neurobiology (T.K., K.-I.M., M.K.), Kyoto
Prefectural University of Medicine Graduate School of Medical Science, Kyoto 602-5586, Japan; and Department of
Regenerative Dermatology (S.In., S.It.), Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan
Context/Objective:
Androgen induces androgenetic alopecia (Androgenetic Alopecia), which has a regressive effect
on hair growth from the frontal region of the scalp. Conversely, Wnt proteins are known to
positivelyaffectmammalianhairgrowth.Wehypothesizedthatandrogenreduceshairgrowthvia
an interaction with the Wnt signaling system. The objective of this study was to investigate the
effect of androgen on Wnt signaling in dermal papilla (DP) cells.
Design:
The effect of androgen and Wnt3a on keratinocyte proliferation was measured by use of a
coculturesystemconsistingofDPcellsandkeratinocytes.Themolecularmechanismsofandrogenand
Wnt pathway interactions in DP cells were examined by analyzing the expression, intracellular local-
ization, and activity of the androgen receptor (AR) and also downstream Wnt signaling molecules.
Results:
Wnt3a-dependent keratinocyte growth was suppressed by the addition of dihydrotest-
osterone in coculture with DP cells that were derived from Androgenetic Alopecia patients, but growth was not
suppressed in coculture with DP cells from non-Androgenetic Alopecia males. Whereas DP cells from both scalp
regions expressed AR protein, the expression levels of AR and cotranslocation with
-catenin, a
downstreamWntsignalingmolecule,werehigherinDPcellso***ApatientsthaninDPcellsfrom
non-Androgenetic Alopecia males. In addition, significant suppression of Wnt signal-mediated transcription in re-
sponse to dihydrotestosterone treatment was observed only in DP cells from Androgenetic Alopecia patients.