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.

Liver X receptors are required for thymic resilience and T cell output

“…Hence, absence of TEC-specific LXRs impaired TEC self-renewal, leading to progressive TEC disappearance and thymic involution. Scds are enzymes that catalyze the production of monounsaturated fatty acids from saturated fatty acids, thus generating essential cell membrane components ( Paton and Ntambi, 2009 ) that are in high demand during cell growth and mitosis ( Coomans de Brachène et al, 2017 ; Igal, 2011 ; Yee et al, 2013 ). Our study therefore suggests that absence of LXRs in TECs impairs Scd-dependent proliferation not necessarily because Scds are obligate orchestrators of the cell cycle, but rather because Scds provide the building blocks without which a cell’s growth and reproduction is compromised.…”

SCD1 activity promotes cell migration via a PLD-mTOR pathway in the MDA-MB-231 triple-negative breast cancer cell line

“…Though the effect of OA on MDA-MB-231 cell behavior was dependent on PLD activity, and could result from an activation of PLD2 by OA, we cannot exclude the possibility that SCD1 and PLD could also act on TNBC cell migration through parallel pathways, some of which have been suggested. For example, through lipid desaturation, SCD1 could influence cell membrane fluidity and signaling activity [54], which might in turn affect cell migration independently of PLD. OA has also been reported to be involved in other phospholipase-dependent signaling pathways stimulating MDA-MB-231 cell migration.…”

Comparative Transcriptomic and Proteomic Analyses Identify Key Genes Associated With Milk Fat Traits in Chinese Holstein Cows

“…PDGF belongs to the same protein family as vascular endothelial growth factors, which play an essential role in the regulation of embryonic development; cell proliferation, migration, and survival; and chemotaxis. PDGF is also involved in the synthesis of monounsaturated FAs in cells (De Brachene et al, 2017). SYBU encodes a microtubule-associated protein that mediates anterograde transport of vesicles to neuronal processes.…”