Suppression of hyaluronan synthase 2 expression reflects the  atrophogenic potential of glucocorticoids.
We recently demonstrated that dexamethasone, a strongly atrophogenic glucocorticoid (GC), downregulated hyaluronan (HA) production in human keratinocytes and fibroblasts in vitro and after topical application to human skin in vivo via suppression of hyaluronan synthase 2 (HAS2). To test whether HAS2 activity might discriminate the atrophogenic potential of other substances applied topically to skin, we compared the HA metabolism in cultured human fibroblasts following in vitro treatment with GCs and the non-atrophogenic calcineurin inhibitor tacrolimus. GCs suppressed HAS2 mRNA expression and decreased HA as shown by qRT-PCR or ELISA. Tacrolimus did not affect hyaluronan-metabolizing enzymes nor total HA. Neither mometasone nor tacrolimus affected the expression of collagen mRNAs in human fibroblasts. In conclusion, suppression of HAS2 activity may represent an early process of GC-induced skin atrophy that precedes the suppression of collagens. Analysis of HAS2 regulation may thus be of value to assess the atrophogenic potential of drugs being developed.
Averbeck
Marco
M
Gebhardt
Carl
C
Anderegg
Ulf
U
Simon
Jan C
JC
D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D014453:Glucuronosyltransferase / Q000378:metabolism*; D006801:Humans; D000076002:Hyaluronan Synthases; D006820:Hyaluronic Acid / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology
D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D006820:Hyaluronic Acid; D003094:Collagen; D014453:Glucuronosyltransferase; C101754:HAS2 protein, human; D000076002:Hyaluronan Synthases; D016559:Tacrolimus