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PMID:22170488

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Citation

Mantel, A, Carpenter-Mendini, AB, Vanbuskirk, JB, De Benedetto, A, Beck, LA and Pentland, AP (2012) Aldo-keto reductase 1C3 is expressed in differentiated human epidermis, affects keratinocyte differentiation, and is upregulated in atopic dermatitis. J. Invest. Dermatol. 132:1103-10

Abstract

Aldo-keto reductase 1C3 (AKR1C3) has been shown to mediate the metabolism of sex hormones and prostaglandin D(2) (PGD(2)), a lipid mediator that promotes skin inflammation in atopic dermatitis (AD). As both have a role in skin function and pathology, we first sought to investigate the expression pattern of AKR1C3 in normal human epidermis. Immunofluorescence revealed a strong expression of AKR1C3 in the differentiated suprabasal layers compared with the basal layer. Western blot analysis and quantitative PCR confirmed that AKR1C3 expression was also upregulated in differentiation-induced primary human keratinocytes (PHKs). To investigate the functional role of AKR1C3 during PHK differentiation, its expression and activity (measured as PGD(2) reduction to 9α,11β-PGF(2) by ELISA) were impaired by small interfering RNA or 2'-hydroxyflavanone, respectively. Cytokeratin 10 (K10) and loricrin expression were then examined by western blot analysis, thus revealing altered expression of these differentiation markers. Finally, following an observation that the AD-associated mediator, PGD(2), upregulated AKR1C3 expression in PHKs, we used immunofluorescence to examine AKR1C3 expression in AD and psoriasis lesions. AKR1C3 was found to be upregulated in AD but not in psoriasis lesions compared with non-lesional skin. Our work demonstrates a function for AKR1C3 in differentiation-associated gene regulation and also suggests a role in supporting inflammation in AD.

Links

PubMed PMC3305848 Online version:10.1038/jid.2011.412

Keywords

3-Hydroxysteroid Dehydrogenases/genetics; 3-Hydroxysteroid Dehydrogenases/metabolism; Biological Markers/metabolism; Calcium/metabolism; Cell Differentiation/drug effects; Cell Differentiation/physiology; Cells, Cultured; Dermatitis, Atopic/metabolism; Dermatitis, Atopic/pathology; Dermatitis, Atopic/physiopathology; Epidermis/cytology; Epidermis/drug effects; Epidermis/metabolism; Flavanones/pharmacology; Gene Expression Regulation/drug effects; Humans; Hydroxyprostaglandin Dehydrogenases/genetics; Hydroxyprostaglandin Dehydrogenases/metabolism; Keratin-10/metabolism; Keratinocytes/cytology; Keratinocytes/drug effects; Keratinocytes/metabolism; Membrane Proteins/metabolism; Prostaglandin D2/metabolism; RNA, Small Interfering/pharmacology; Up-Regulation/drug effects; Up-Regulation/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:K1C10

involved_in

GO:0030216: keratinocyte differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:K1C10

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:K2C5

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:AK1C3

involved_in

GO:0030216: keratinocyte differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AK1C3

located_in

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0002026)
  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:AK1C3

part_of

GO:0005737: cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(UBERON:0002026)
  • part_of:(CL:0000312)

Seeded From UniProt

complete

HUMAN:AK1C3

involved_in

GO:0030216: keratinocyte differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

happens_during:(GO:0071277)

Seeded From UniProt

complete

HUMAN:AK1C3

enables

GO:0047020: 15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:AK1C3

involved_in

GO:0071277: cellular response to calcium ion

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:AK1C3

involved_in

GO:0071379: cellular response to prostaglandin stimulus

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

See also

References

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