Expression of the homeobox gene, HOPX, is modulated by cell differentiation in human keratinocytes and is involved in the expression of differentiation markers.
Homeodomain only protein X (HOPX), an unusual homeodomain protein, was originally identified as a key regulator of cardiac development. We first demonstrated that the expression of HOPX was dependent on the differentiation of human keratinocytes and has an effect on the expression of differentiation markers. HOPX was suppressed in proliferating human keratinocytes and was gradually induced by calcium-triggered differentiation of human keratinocytes. In the epidermis, HOPX is highly expressed in the terminally differentiated suprabasal layers. Among the transcript variants of HOPX, the variant 3 driven by promoter A was the main transcript and it was regulated by cell differentiation in human keratinocytes. The expression of HOPX was induced through the phorbol-12-myristate-13-acetate (PMA)-dependent protein kinase C (PKC) signaling pathway, and not by the demethylating agent, 5-aza-dC (5-aza-2'-deoxycitidine) suggesting the suppression of HOPX is not associated with DNA methylation in human keratinocytes. The RNA interference (RNAi) silencing experiment showed that the knockdown of HOPX expression resulted in the increase of such differentiation markers as involucrin and loricrin. Exogenous expression of HOPX down-regulated the expression of differentiation marker genes in immortalized human keratinocytes (HaCaT). Collectively, HOPX is modulated by cell differentiation in human keratinocytes and this might contribute to homeostasis of keratinocytes by controlling differentiation-dependent genes.
Yang
Jun-Mo
JM
Department of Dermatology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, South Korea.
Sim
Seon Mi
SM
Kim
Hyo-Yeon
HY
Park
Geon Tae
GT
D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D002478:Cells, Cultured; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000378:metabolism; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology / Q000378:metabolism
D018398:Homeodomain Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; C064554:loricrin; C032253:involucrin