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.
Highlights
Alexandra Coomans de Brachene1, Nicolas Dif1, Audrey de Rocca Serra1, Chloe Bonnineau2, Amelie I
These results show that the up-regulation of Stearoyl-coenzyme A desaturase (SCD) expression by platelet-derived growth factor (PDGF) correlates with an increased proportion of monounsaturated fatty acids (MUFA) in fibroblasts
We demonstrate that SCD is an important mediator of growth factor-induced proliferation of normal human fibroblasts
Summary
Alexandra Coomans de Brachene, Nicolas Dif, Audrey de Rocca Serra, Chloe Bonnineau, Amelie I. Stearoyl-coenzyme A desaturase (SCD) catalyzes the D9-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. Our data suggest that SCD is required for the response of normal fibroblasts to growth factors Growth factors, such as the platelet-derived growth factor (PDGF), are important mediators of cellular processes such as cell proliferation, migration, survival, and differentiation [1]. MTORC1 controls protein synthesis by regulating translation and activates the sterol regulatory elementbinding protein (SREBP), a lipogenic transcription factor This factor regulates the expression of virtually all lipogenic enzymes involved in cholesterol, fatty acid, and phospholipid synthesis, such as 3-hydroxy-3methylglutaryl-coenzyme A synthase (HMGCS1), Abbreviations MEM, minimum essential medium; MUFA, monounsaturated fatty acids; PDGF, platelet-derived growth factor; PI3K, phosphatidylinositol 3kinase; SCD, stearoyl-coenzyme A desaturase; SFA, saturated fatty acids; shSCD, small-hairpin RNA against SCD. A second human gene, SCD5, is expressed only in the brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
