title: PDGF-induced fibroblast growth requires monounsaturated fatty acid production by stearoyl-CoA desaturase.
abstract: Stearoyl-coenzyme A desaturase (SCD) catalyzes the Δ9-cis desaturation of saturated fatty acids (SFA) to generate monounsaturated fatty acids (MUFA). This enzyme is highly up-regulated by platelet-derived growth factor (PDGF) in human fibroblasts. Accordingly, the analysis of cellular fatty acids by gas chromatography showed that PDGF significantly increased the proportion of MUFA, particularly palmitoleate, in cellular lipids. To further analyze the role of SCD in fibroblasts, we used small hairpin RNA targeting SCD (shSCD), which decreased the MUFA content. SCD down-regulation blunted the proliferation of fibroblasts in response to PDGF. This was confirmed using a pharmacological inhibitor of SCD. In addition, proliferation was blocked by palmitate and stearate (two SCD substrates) but not by palmitoleate and oleate (two SCD products). In the presence of an equal amount of oleate, palmitate had no effect on cell proliferation. SCD inhibition or down-regulation did not decrease PDGF receptor activity or signaling. However, by measuring plasma membrane lipid lateral diffusion by fluorescence recovery after photobleaching, we showed that the modulation of the MUFA/SFA ratio by PDGF and SCD inhibitor was related to modifications of membrane fluidity. Altogether, our data suggest that SCD is required for the response of normal fibroblasts to growth factors.
authors.affiliation: de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Coomans de Brachène
authors.affiliation: de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Dif
authors.affiliation: de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.
authors.forename: Audrey
authors.initials: A
authors.lastname: de Rocca Serra
authors.affiliation: Institute of Life Sciences Université catholique de Louvain Louvain-La-Neuve Belgium.
authors.forename: Chloé
authors.initials: C
authors.lastname: Bonnineau
authors.affiliation: de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.
authors.forename: Amélie I
authors.initials: AI
authors.lastname: Velghe
authors.affiliation: Institute of Life Sciences Université catholique de Louvain Louvain-La-Neuve Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Larondelle
authors.affiliation: de Duve Institute CELL unit Université catholique de Louvain Brussels Belgium.
authors.forename: Donatienne
authors.initials: D
authors.lastname: Tyteca
authors.affiliation: de Duve Institute MEXP unit Université catholique de Louvain Brussels Belgium.
authors.forename: Jean-Baptiste
authors.identifier: 0000-0002-8016-6689
authors.initials: JB
authors.lastname: Demoulin
keywords: PDGFB; PDGFRB; SCD1; oleic acid; palmitic acid