The regulation of stearoyl-CoA desaturase (SCD), a rate-limiting enzyme in the synthesis of unsaturated fatty acids, is physiologically important because the ratio of saturated to unsaturated fatty acids is thought to control cellular functions by modulating the structural integrity and fluidity of cell membranes. Transforming growth factor-beta (TGF-beta), a multifunctional cytokine, increased SCD mRNA expression in cultured human retinal pigment epithelial cells. This response was elicited by all three TGF-beta isoforms, beta1, beta2, and beta3. However, SCD mRNA expression was not increased either by other members of the TGF-beta family or by other growth factors or cytokines. TGF-beta also increased SCD mRNA expression in several other cell lines tested. The increase in SCD mRNA expression was preceded by a marked increase in Smad2 phosphorylation in TGF-beta-treated human retinal pigment epithelial cells. TGF-beta did not induce SCD mRNA expression in a Smad4-deficient cell line. However, Smad4 overexpression restored the TGF-beta effect in this cell line. Moreover, TGF-beta-induced SCD mRNA expression was effectively blocked by the overexpression of Smad7, an inhibitory Smad. Thus, a TGF-beta signal transduction pathway involving Smad proteins appears to regulate the cellular expression of the SCD gene, and this regulation may play an important role in lipid metabolism.
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http://dx.doi.org/10.1074/jbc.M108730200 | DOI Listing |
Adv Sci (Weinh)
November 2024
Translational Neuroscience Facility, Department of Physiology, School of Biomedical Sciences, Graduate School of Biomedical Engineering, Tyree Institute for Health Engineering (IHealthE), UNSW, Sydney, NSW, 2052, Australia.
Viral vector and lipid nanoparticle based gene delivery have limitations around spatiotemporal control, transgene packaging size, and vector immune reactivity, compromising translation of nucleic acid (NA) therapeutics. In the emerging field of DNA and particularly RNA-based gene therapies, vector-free delivery platforms are identified as a key unmet need. Here, this work addresses these challenges through gene electrotransfer (GET) of "naked" polyanionic DNA/mRNA using a single needle form-factor which supports "electro-lens" based compression of the local electric field, and local control of tissue conductivity, enabling single capacitive discharge minimal charge gene delivery.
View Article and Find Full Text PDFBackground: Fibroinflammatory cholangiopathies, such as primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC), are characterized by inflammation and biliary fibrosis, driving disease-related complications. In biliary fibrosis, cholangiocytes activated by transforming growth factor-β (TGFβ) release signals that recruit immune cells to drive inflammation and activate hepatic myofibroblasts to deposit the extracellular matrix (ECM). TGFβ regulates stearoyl-CoA desaturase (SCD), an enzyme that catalyzes the synthesis of monounsaturated fatty acids, in stimulating fibroinflammatory lipid signaling.
View Article and Find Full Text PDFSweet pepper, a globally commercialized horticultural crop, has been demonstrated to impede fat accumulation, but its mechanism remains incompletely understood. This study was designed to explore the potential mechanism of sweet pepper in reducing fat accumulation in through RNA-seq and metabolome analysis. A total of 22 metabolites were identified from sweet pepper by UHPLC-ESI-TOF-MS analysis.
View Article and Find Full Text PDFAging (Albany NY)
November 2024
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
People living with sickle cell disease (SCD) experience complications indicative of an accelerated aging phenotype typified by early decline in physical function and increased risk for age-related conditions. Cellular senescence, measured by expression of p16 in peripheral T-lymphocytes, is recognized as one of the underlying contributors to organismal aging. To examine if cellular senescence is increased in SCD patients, we cross-sectionally measured and compared expression of p16 mRNA in peripheral blood T lymphocytes in 18 adolescents and young adults with SCD to 27 similarly aged individuals without SCD.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), 30120 Murcia, Spain.
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