Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes.
Regulation of the Glycerol Transporter, Aquaporin-3, by Histone Deacetylase-3 and p53 in Keratinocytes.
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DOI:
10.1016/j.jid.2017.04.031
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发表时间:
2017-09
期刊:
影响因子:
--
通讯作者:
Bollag WB
中科院分区:
文献类型:
--
作者:
Choudhary V;Olala LO;Kagha K;Pan ZQ;Chen X;Yang R;Cline A;Helwa I;Marshall L;Kaddour-Djebbar I;McGee-Lawrence ME;Bollag WB
Aquaporin-3 (AQP3), a water and glycerol channel, plays an important role in epidermal function, with studies demonstrating its involvement in keratinocyte proliferation, differentiation and migration and epidermal wound healing and barrier repair. Increasing speculation about the use of histone deacetylase (HDAC) inhibitors to treat skin diseases led us to investigate HDAC’s role in the regulation of AQP3. The broad-spectrum HDAC inhibitor, suberolyanilide hydroxamic acid (SAHA) induced AQP3 mRNA and protein expression in a dose- and time- dependent manner in normal keratinocytes. The SAHA-induced increase in AQP3 levels resulted in enhanced [3H]glycerol uptake in normal but not in AQP3 knockout keratinocytes, confirming that the expressed AQP3 was functional. Utilization of HDAC inhibitors with different specificities limited our exploration of the responsible HDAC member to HDAC1, HDAC2 or HDAC3. Cre-recombinase-mediated knockdown and overexpression of HDAC3 suggested a role for HDAC3 in suppressing AQP3 expression basally. Further investigation implicated p53 as a transcription factor involved in regulating HDAC inhibitor-induced AQP3 expression. Thus, our study supports the regulation of AQP3 expression by HDAC3 and p53. Since SAHA is already approved to treat cutaneous T-cell lymphoma, it could potentially be used as a novel therapy for skin diseases like psoriasis, where AQP3 is abnormally expressed.
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影响因子:
8
作者:
Arun, S. N.;Kaddour-Djebbar, I.;Shapiro, B. A.;Bollag, W. B.
通讯作者:
Bollag, W. B.
影响因子:
4.6
作者:
Choudhary V;Olala LO;Kaddour-Djebbar I;Helwa I;Bollag WB
通讯作者:
Bollag WB
影响因子:
4.8
作者:
Hara, M;Ma, TH;Verkman, AS
通讯作者:
Verkman, AS
影响因子:
4
作者:
Codelia, Veronica A.;Cisterna, Matias;Moreno, Ricardo D.
通讯作者:
Moreno, Ricardo D.
DOI:
10.1186/1756-9966-33-38
发表时间:
2014-05-03
期刊:
Journal of experimental & clinical cancer research : CR
影响因子:
--
作者:
Chen J;Wang T;Zhou YC;Gao F;Zhang ZH;Xu H;Wang SL;Shen LZ
通讯作者:
Shen LZ