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PDGF‐induced fibroblast growth requires monounsaturated fatty acid production by stearoyl‐CoA desaturase
Author(s) -
Coomans de Brachène Alexandra,
Dif Nicolas,
Rocca Serra Audrey,
Bonnineau Chloé,
Velghe Amélie I.,
Larondelle Yvan,
Tyteca Donatienne,
Demoulin JeanBaptiste
Publication year - 2017
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.12194
Subject(s) - platelet derived growth factor receptor , chemistry , coenzyme a , growth factor , platelet derived growth factor , fatty acid , biochemistry , cell growth , fibroblast , receptor , enzyme , reductase , in vitro
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 (sh SCD ), 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.

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