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Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes.

Fujishita K, Koizumi S, Inoue K - Purinergic Signal. (2006)

Bottom Line: The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs.Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs.This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling.

View Article: PubMed Central - PubMed

Affiliation: Division of Biosignaling, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo, Japan.

ABSTRACT
Retinoids, vitamin A derivatives, are important regulators of the growth and differentiation of skin cells. Although retinoids are therapeutically used for several skin ailments, little is known about their effects on P2 receptors, known to be involved in various functions in the skin. DNA array analysis showed that treatment of normal human epidermal keratinocytes (NHEKs) with all-trans-retinoic acid (ATRA), an agonist to RAR (retinoic acid receptor), enhanced the expression of mRNA for the P2Y2 receptor, a metabotropic P2 receptor that is known to be involved in the proliferation of the epidermis. The expression of other P2 receptors in NHEKs was not affected by ATRA. ATRA increased the mRNA for the P2Y2 receptor in a concentration-dependent fashion (1 nM to 1 muM). Am80, a synthesized agonist to RAR, showed a similar enhancement, whereas 9-cis-retinoic acid (9-cisRA), an agonist to RXR (retinoid X receptor), enhanced P2Y2 gene expression to a lesser extent. Ca(2+) imaging analysis showed that ATRA also increased the function of P2Y2 receptors in NHEKs. Retinoids are known to enhance the turnover of the epidermis by increasing both proliferation and terminal differentiation. The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs. Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs. This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling.

No MeSH data available.


Related in: MedlinePlus

Changes in mRNA expression for P2Y receptors induced by ATRA in NHEKs. Diagram shows the percentage of the quantity after amplification by real-time RT-PCR for P2Y1, P2Y2 and P2Y11 receptor mRNAs extracted from NHEKs treated with 1 µM ATRA for 2 h. Asterisks show significant difference from control groups (white columns, **P < 0.01). mRNAs of P2Y2 receptors were increased by more than twofold vs. control. Data were obtained from at least three independent experiments.
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Fig1: Changes in mRNA expression for P2Y receptors induced by ATRA in NHEKs. Diagram shows the percentage of the quantity after amplification by real-time RT-PCR for P2Y1, P2Y2 and P2Y11 receptor mRNAs extracted from NHEKs treated with 1 µM ATRA for 2 h. Asterisks show significant difference from control groups (white columns, **P < 0.01). mRNAs of P2Y2 receptors were increased by more than twofold vs. control. Data were obtained from at least three independent experiments.

Mentions: The skin expresses multiple P2 receptors. We previously showed that the expression of P2Y1, P2Y2 and P2Y11 is relatively higher in NHEKs [16]. Firstly, we examined the changes in the mRNAs for the P2 receptors induced by retinoids in NHEKs using DNA array analysis. Unfortunately, the DNA microarray we used (U95A GeneChip DNA microarray) does not contain all cloned P2 receptor genes (for example, P2Y11 receptors) but it contains P2Y1, P2Y2, P2Y6, P2X1, P2X3, P2X4, P2X5 and P2X7 receptor genes. Treatment of NHEKs with 0.1 µM all-trans retinoic acid (ATRA) for 6 h caused a drastic increase in the mRNA for P2Y2 receptor (304.1 ± 38.1% of control, n = 3). Interestingly, ATRA did not affect the expression of any other P2 receptors included in U95A GeneChip (Table 1), suggesting that ATRA selectively upregulates P2Y2 receptors in NHEKs. This result was confirmed quantitatively using real-time RT-PCR (Figure 1). Treatment of NHEKs with ATRA induced a similar increase in the mRNA for P2Y2 receptors (264.4 ± 59.1% of control, n = 3) but not for other P2 receptors such as P2Y1 and P2Y11 (P2Y1, 67.5 ± 6.67, n = 3; P2Y11, 70.0 ± 11.7% of control, n = 3).Figure 1


Upregulation of P2Y2 receptors by retinoids in normal human epidermal keratinocytes.

Fujishita K, Koizumi S, Inoue K - Purinergic Signal. (2006)

Changes in mRNA expression for P2Y receptors induced by ATRA in NHEKs. Diagram shows the percentage of the quantity after amplification by real-time RT-PCR for P2Y1, P2Y2 and P2Y11 receptor mRNAs extracted from NHEKs treated with 1 µM ATRA for 2 h. Asterisks show significant difference from control groups (white columns, **P < 0.01). mRNAs of P2Y2 receptors were increased by more than twofold vs. control. Data were obtained from at least three independent experiments.
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Related In: Results  -  Collection

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Fig1: Changes in mRNA expression for P2Y receptors induced by ATRA in NHEKs. Diagram shows the percentage of the quantity after amplification by real-time RT-PCR for P2Y1, P2Y2 and P2Y11 receptor mRNAs extracted from NHEKs treated with 1 µM ATRA for 2 h. Asterisks show significant difference from control groups (white columns, **P < 0.01). mRNAs of P2Y2 receptors were increased by more than twofold vs. control. Data were obtained from at least three independent experiments.
Mentions: The skin expresses multiple P2 receptors. We previously showed that the expression of P2Y1, P2Y2 and P2Y11 is relatively higher in NHEKs [16]. Firstly, we examined the changes in the mRNAs for the P2 receptors induced by retinoids in NHEKs using DNA array analysis. Unfortunately, the DNA microarray we used (U95A GeneChip DNA microarray) does not contain all cloned P2 receptor genes (for example, P2Y11 receptors) but it contains P2Y1, P2Y2, P2Y6, P2X1, P2X3, P2X4, P2X5 and P2X7 receptor genes. Treatment of NHEKs with 0.1 µM all-trans retinoic acid (ATRA) for 6 h caused a drastic increase in the mRNA for P2Y2 receptor (304.1 ± 38.1% of control, n = 3). Interestingly, ATRA did not affect the expression of any other P2 receptors included in U95A GeneChip (Table 1), suggesting that ATRA selectively upregulates P2Y2 receptors in NHEKs. This result was confirmed quantitatively using real-time RT-PCR (Figure 1). Treatment of NHEKs with ATRA induced a similar increase in the mRNA for P2Y2 receptors (264.4 ± 59.1% of control, n = 3) but not for other P2 receptors such as P2Y1 and P2Y11 (P2Y1, 67.5 ± 6.67, n = 3; P2Y11, 70.0 ± 11.7% of control, n = 3).Figure 1

Bottom Line: The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs.Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs.This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling.

View Article: PubMed Central - PubMed

Affiliation: Division of Biosignaling, National Institute of Health Science, 1-18-1 Kamiyoga, Setagaya, Tokyo, Japan.

ABSTRACT
Retinoids, vitamin A derivatives, are important regulators of the growth and differentiation of skin cells. Although retinoids are therapeutically used for several skin ailments, little is known about their effects on P2 receptors, known to be involved in various functions in the skin. DNA array analysis showed that treatment of normal human epidermal keratinocytes (NHEKs) with all-trans-retinoic acid (ATRA), an agonist to RAR (retinoic acid receptor), enhanced the expression of mRNA for the P2Y2 receptor, a metabotropic P2 receptor that is known to be involved in the proliferation of the epidermis. The expression of other P2 receptors in NHEKs was not affected by ATRA. ATRA increased the mRNA for the P2Y2 receptor in a concentration-dependent fashion (1 nM to 1 muM). Am80, a synthesized agonist to RAR, showed a similar enhancement, whereas 9-cis-retinoic acid (9-cisRA), an agonist to RXR (retinoid X receptor), enhanced P2Y2 gene expression to a lesser extent. Ca(2+) imaging analysis showed that ATRA also increased the function of P2Y2 receptors in NHEKs. Retinoids are known to enhance the turnover of the epidermis by increasing both proliferation and terminal differentiation. The DNA microarray analysis also revealed that ATRA upregulates various genes involved in the differentiation of NHEKs. Our present results suggest that retinoids, at least in part, exert their proliferative effects by upregulating P2Y2 receptors in NHEKs. This effect of retinoids may be closely related to their therapeutic effect against various ailments or aging events in skins such as over-keratinization, pigmentation and re-modeling.

No MeSH data available.


Related in: MedlinePlus