Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases.
Remodeling of the dermal extracellular matrix occurs during photoaging. Here, the effect of repetitive UVB irradiation on dermal hyaluronic acid (HA) was examined. C57/BL6 mice were chronically (182 days) irradiated with UVB, and consecutive skin biopsies were collected during the irradiation period and afterward (300 and 400 days of age). UVB caused marked loss of HA from the papillary dermis and down-regulation of HA synthase 1 (HAS1), HAS2, and HAS3 mRNA expression. In contrast, hyaluronidases (HYAL) 1, HYAL2, and HA receptor CD44 were unchanged. Furthermore, transforming growth factor beta-1 (TGF-beta1) and TGF-beta1-receptor II expression were decreased in UVB-irradiated biopsies, and TGF-beta1 strongly induced HAS1 and HAS2 expression in cultured dermal fibroblasts. Therefore, TGF-beta1 might be one factor involved in UVB-induced down-regulation of HAS enzymes. In addition, total cell number and the percentage of proliferating fibroblasts in the papillary dermis of UVB-irradiated mice were decreased. Down-regulation of HAS2 by lentiviral overexpression of short hairpin RNA in vitro caused inhibition of HA synthesis, DNA synthesis, and migration of dermal fibroblasts. In conclusion, chronic UVB irradiation induces loss of HA from the dermis, thereby contributing to the quiescent phenotype of dermal fibroblasts.
Dai
Guang
G
Molekulare Pharmakologie, Institut für Pharmakologie and Klinische Pharmakologie, Universitätsklinkum Düsseldorf, Düsseldorf, Germany.
Freudenberger
Till
T
Zipper
Petra
P
Melchior
Ariane
A
Grether-Beck
Susanne
S
Rabausch
Berit
B
de Groot
Jens
J
Twarock
Sören
S
Hanenberg
Helmut
H
Homey
Bernhard
B
Krutmann
Jean
J
Reifenberger
Julia
J
Fischer
Jens W
JW
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis; D020405:Dermis / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D015536:Down-Regulation; D005347:Fibroblasts / Q000378:metabolism / Q000502:physiology / Q000528:radiation effects; D014453:Glucuronosyltransferase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
C476399:Cd44 protein, mouse; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; D014453:Glucuronosyltransferase; C491099:Has2 protein, mouse; C491356:Has3 protein, mouse; D000076002:Hyaluronan Synthases; D006821:Hyaluronoglucosaminidase