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Article

The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades

1
Center for Bioscience Research & Education, Utsunomiya University, Tochigi 321-8505, Japan
2
School of Bioscience and Biotechnology, Tokyo University of Technology, Tokyo 192-0982, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editor: Alessandro Terrinoni
Int. J. Mol. Sci. 2021, 22(4), 2057; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042057
Received: 26 December 2020 / Revised: 9 February 2021 / Accepted: 16 February 2021 / Published: 19 February 2021
(This article belongs to the Special Issue Molecular Mechanisms of Skin Aging and Atopic Dermatitis)
Little is known about the effects on hyaluronan (HA) metabolism of UVA radiation. This study demonstrates that the secretion of HA by human dermal fibroblasts (HDFs) is downregulated by UVA, accompanied by the down- and upregulation of mRNA and protein levels of the HA-synthesizing enzyme (HAS2) and the HA-degrading protein, HYaluronan Binding protein Involved in HA Depolymerization(HYBID), respectively. Signaling analysis revealed that the exposure distinctly elicits activation of the p38/MSK1/CREB/c-Fos/AP-1 axis, the JNK/c-Jun axis, and the p38/ATF-2 axis, but downregulates the phosphorylation of NF-kB and JAK/STAT3. A signal inhibition study demonstrated that the inhibition of p38 significantly abrogates the UVA-accentuated mRNA level of HYBID. Furthermore, the inhibition of STAT3 significantly downregulates the level of HAS2 mRNA in non-UVA exposed HDFs. Analysis using siRNAs demonstrated that transfection of ATF-2 siRNA but not c-Fos siRNA abrogates the increased protein level of HYBID in UVA-exposed HDFs. An inhibitor of protein tyrosine phosphatase but not of protein serine/threonine phosphatase restored the diminished phosphorylation level of STAT3 at Tyr 705, accompanied by a significant abolishing effect on the decreased mRNA expression level of HAS2. Silencing with a protein tyrosine phosphatase PTP-Meg2 siRNA revealed that it abrogates the decreased phosphorylation of STAT3 at Tyr 705 in UVA-exposed HDFs. These findings suggest that the UVA-induced decrease in HA secretion by HDFs is attributable to the down- and upregulation of HAS2 and HYBID expression, respectively, changes that are mainly ascribed to the inactivated signaling of the STAT3 axis due to the activated tyrosine protein phosphatase PTP-Meg2 and the activated signaling of the p38/ATF2 axis, respectively. View Full-Text
Keywords: ultraviolet A; hyaluronan; human dermal fibroblasts; hyaluronan synthases; HYaluronan Binding protein Involved in HA Depolymerization ultraviolet A; hyaluronan; human dermal fibroblasts; hyaluronan synthases; HYaluronan Binding protein Involved in HA Depolymerization
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MDPI and ACS Style

Terazawa, S.; Takada, M.; Sato, Y.; Nakajima, H.; Imokawa, G. The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades. Int. J. Mol. Sci. 2021, 22, 2057. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042057

AMA Style

Terazawa S, Takada M, Sato Y, Nakajima H, Imokawa G. The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades. International Journal of Molecular Sciences. 2021; 22(4):2057. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042057

Chicago/Turabian Style

Terazawa, Shuko; Takada, Mariko; Sato, Yoriko; Nakajima, Hiroaki; Imokawa, Genji. 2021. "The Attenuated Secretion of Hyaluronan by UVA-Exposed Human Fibroblasts Is Associated with Up- and Downregulation of HYBID and HAS2 Expression via Activated and Inactivated Signaling of the p38/ATF2 and JAK2/STAT3 Cascades" Int. J. Mol. Sci. 22, no. 4: 2057. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22042057

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