PMID- 30792099
OWN - NLM
STAT- MEDLINE
DCOM- 20191002
LR  - 20191002
IS  - 1873-569X (Electronic)
IS  - 0923-1811 (Linking)
VI  - 93
IP  - 3
DP  - 2019 Mar
TI  - Androgens modulate keratinocyte differentiation indirectly through enhancing 
      growth factor production from dermal fibroblasts.
PG  - 150-158
LID - S0923-1811(19)30024-6 [pii]
LID - 10.1016/j.jdermsci.2019.01.007 [doi]
AB  - BACKGROUND: The main pathogenesis of acne vulgaris is increase in sebum 
      production and abnormal keratinization of the hair infundibulum. The androgens 
      are involved in acne pathogenesis by modulating sebaceous glands to enhance sebum 
      production. However, the molecular mechanisms of abnormal keratinization of the 
      hair infundibulum are not fully elucidated. OBJECTIVE: We hypothesized that the 
      androgens affect the dermal fibroblasts, another androgen receptor-positive cells 
      in the skin, resulting in abnormal keratinization through keratinocyte-fibroblast 
      interaction. METHODS: We investigated effects of androgens and estrogens on 
      growth factors expressions by RT-PCR and western blot analysis in human 
      fibroblast (hFB), human keratinocyte (hKC), and fibroblast-keratinocyte 
      co-culture. In vivo, we examined the growth factor expression in acne lesions 
      compared to normal hair follicles by laser-assisted confocal microscope. RESULTS: 
      In vitro, androgens but not estrogens significantly increased amphiregulin 
      (AREG), epiregulin (EREG), fibroblast growth factor (FGF) 10, and insulin-like 
      growth factor binding protein (IGFBP) 5 mRNA and protein expressions in human 
      fibroblasts but not in keratinocytes. In vivo, AREG, EREG, FGF10, and IGFBP5 were 
      more abundant in acne lesion compared to normal facial skin. FGF10 suppressed 
      cytokeratin 1 and cytokeratin 10 expression in hKC, which was along with the 
      decreased ratio of cytokeratin 10 against cytokeratin 14 in acne lesions compared 
      to normal facial skin. Also, DHT suppressed cytokeratin 1 and cytokeratin 10, in 
      fibroblast-keratinocyte co-culture similarly to the effect of FGF10 to hKC. 
      CONCLUSION: These observations suggested that androgens enhance growth factors 
      production from dermal fibroblasts, and growth factors from fibroblasts alter 
      keratinocyte differentiation in acne lesion.
CI  - Copyright (c) 2019 Japanese Society for Investigative Dermatology. Published by 
      Elsevier B.V. All rights reserved.
FAU - Kumtornrut, Chanat
AU  - Kumtornrut C
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, 980-8575, Japan; Division of Dermatology, Department of Medicine, Faculty 
      of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand.
FAU - Yamauchi, Takeshi
AU  - Yamauchi T
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, 980-8575, Japan.
FAU - Koike, Saaya
AU  - Koike S
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, 980-8575, Japan.
FAU - Aiba, Setsuya
AU  - Aiba S
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, 980-8575, Japan.
FAU - Yamasaki, Kenshi
AU  - Yamasaki K
AD  - Department of Dermatology, Tohoku University Graduate School of Medicine, Sendai, 
      Miyagi, 980-8575, Japan. Electronic address: kyamasaki@med.tohoku.ac.jp.
LA  - eng
PT  - Journal Article
DEP - 20190126
PL  - Netherlands
TA  - J Dermatol Sci
JT  - Journal of dermatological science
JID - 9011485
RN  - 0 (Androgens)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - Acne Vulgaris/*pathology
MH  - Androgens/*metabolism
MH  - Cell Communication/physiology
MH  - Cell Differentiation/physiology
MH  - Cell Line
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Fibroblasts/*metabolism
MH  - Gene Expression Profiling
MH  - Hair Follicle/cytology
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*metabolism
MH  - Keratinocytes/*pathology
MH  - Sebaceous Glands/cytology/metabolism/pathology
MH  - Sebum/metabolism
OTO - NOTNLM
OT  - Acne
OT  - Androgens
OT  - Fibroblast growth factor 10
OT  - Fibroblasts
OT  - Keratinocyte differentiation
EDAT- 2019/02/23 06:00
MHDA- 2019/10/03 06:00
CRDT- 2019/02/23 06:00
PHST- 2018/10/29 00:00 [received]
PHST- 2018/12/28 00:00 [revised]
PHST- 2019/01/21 00:00 [accepted]
PHST- 2019/02/23 06:00 [pubmed]
PHST- 2019/10/03 06:00 [medline]
PHST- 2019/02/23 06:00 [entrez]
AID - S0923-1811(19)30024-6 [pii]
AID - 10.1016/j.jdermsci.2019.01.007 [doi]
PST - ppublish
SO  - J Dermatol Sci. 2019 Mar;93(3):150-158. doi: 10.1016/j.jdermsci.2019.01.007. Epub 
      2019 Jan 26.