PMID- 17982124 OWN - NLM STAT- MEDLINE DCOM- 20080125 LR - 20220321 IS - 0002-9440 (Print) IS - 1525-2191 (Electronic) IS - 0002-9440 (Linking) VI - 171 IP - 5 DP - 2007 Nov TI - Chronic ultraviolet B irradiation causes loss of hyaluronic acid from mouse dermis because of down-regulation of hyaluronic acid synthases. PG - 1451-61 AB - 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. FAU - Dai, Guang AU - Dai G AD - Molekulare Pharmakologie, Institut fur Pharmakologie and Klinische Pharmakologie, Universitatsklinkum Dusseldorf, Dusseldorf, Germany. FAU - Freudenberger, Till AU - Freudenberger T FAU - Zipper, Petra AU - Zipper P FAU - Melchior, Ariane AU - Melchior A FAU - Grether-Beck, Susanne AU - Grether-Beck S FAU - Rabausch, Berit AU - Rabausch B FAU - de Groot, Jens AU - de Groot J FAU - Twarock, Soren AU - Twarock S FAU - Hanenberg, Helmut AU - Hanenberg H FAU - Homey, Bernhard AU - Homey B FAU - Krutmann, Jean AU - Krutmann J FAU - Reifenberger, Julia AU - Reifenberger J FAU - Fischer, Jens W AU - Fischer JW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Pathol JT - The American journal of pathology JID - 0370502 RN - 0 (Cd44 protein, mouse) RN - 0 (Hyaluronan Receptors) RN - 0 (Isoenzymes) RN - 0 (Receptors, Transforming Growth Factor beta) RN - 0 (Transforming Growth Factor beta1) RN - 9004-61-9 (Hyaluronic Acid) RN - EC 2.4.1.17 (Glucuronosyltransferase) RN - EC 2.4.1.212 (Has2 protein, mouse) RN - EC 2.4.1.212 (Has3 protein, mouse) RN - EC 2.4.1.212 (Hyaluronan Synthases) RN - EC 3.2.1.35 (Hyaluronoglucosaminidase) SB - IM MH - Animals MH - Cell Proliferation MH - Cells, Cultured MH - Chemotaxis MH - Dermis/cytology/metabolism/*radiation effects MH - Down-Regulation MH - Fibroblasts/metabolism/physiology/radiation effects MH - Glucuronosyltransferase/*biosynthesis/genetics MH - Humans MH - Hyaluronan Receptors/metabolism MH - Hyaluronan Synthases MH - Hyaluronic Acid/*metabolism MH - Hyaluronoglucosaminidase/metabolism MH - Isoenzymes/biosynthesis MH - Mice MH - Mice, Inbred C57BL MH - Receptors, Transforming Growth Factor beta/metabolism MH - Transforming Growth Factor beta1/metabolism MH - Ultraviolet Rays/*adverse effects PMC - PMC2043507 EDAT- 2007/11/06 09:00 MHDA- 2008/01/26 09:00 PMCR- 2008/11/01 CRDT- 2007/11/06 09:00 PHST- 2007/11/06 09:00 [pubmed] PHST- 2008/01/26 09:00 [medline] PHST- 2007/11/06 09:00 [entrez] PHST- 2008/11/01 00:00 [pmc-release] AID - S0002-9440(10)62407-8 [pii] AID - 10.2353/ajpath.2007.070136 [doi] PST - ppublish SO - Am J Pathol. 2007 Nov;171(5):1451-61. doi: 10.2353/ajpath.2007.070136.