scholarly journals PPAR γ/Nnat/NF-κB Axis Involved in Promoting Effects of Adiponectin on Preadipocyte Differentiation

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Wenkai Yang ◽  
Wenjin Yuan ◽  
Xinghua Peng ◽  
Meiling Wang ◽  
Jie Xiao ◽  
...  
Keyword(s):  
Protein Expression ◽  
Peroxisome Proliferator ◽  
Preadipocyte Differentiation ◽  
Peroxisome Proliferator Activated Receptor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Expression Levels ◽  
Real Time Quantitative Pcr ◽  
Inflammatory Conditions ◽  
Ppar Γ ◽  
Total Antioxidant

A previous study has demonstrated that adiponectin (APN) could promote preadipocyte differentiation, and the present study further explored its mechanism. 3T3-L1 cells were infected with adenovirus holding human adiponectin gene apM1 and mouse neuronatin (Nnat) shRNA and initiated differentiation while coculturing with mature adipocytes stimulated with LPS. After 8 days, preadipocyte differentiation was observed by Oil Red O staining. Real-time quantitative PCR was used to evaluate mRNA expression levels of monocyte chemoattractant protein-1 (MCP-1), interleukin- (IL-) 6, IL-8, and tumor necrosis factor α (TNF-α). The levels of reactive oxygen species (ROS), total antioxidant capacity (T-AOC), malondialdehyde (MDA), and superoxide dismutase (SOD) in 3T3-L1 cells were detected. Western blotting was done to quantify the protein expression levels of Nnat, peroxisome proliferator-activated receptor (PPAR) γ, p65, and inhibitor of nuclear factor κB (IκB) α. Results demonstrated that APN overexpression markedly increased preadipocyte differentiation; inhibited gene expression of MCP-1, IL-6, IL-8, and TNF-α; reduced ROS and MDA release; increased T-AOC and SOD levels; upregulated Nnat, PPAR γ, and IκB α protein expressions; and downregulated p65 protein expression under LPS stimulation. However, the effects of APN were markedly attenuated when Nnat expression was knocked down. Taken together, the present study provided evidences that the effects of APN on promoting preadipocyte differentiation under inflammatory conditions via anti-inflammation and antioxidative stress may be regulated by the PPAR γ/Nnat/NF-κB signaling pathway.

Stretch reduces nephrin expression via an angiotensin II-AT1-dependent mechanism in human podocytes: effect of rosiglitazone

2010 ◽  
Vol 298 (2) ◽  
pp. F381-F390 ◽  
Author(s):  
Ilaria Miceli ◽  
Davina Burt ◽  
Elena Tarabra ◽  
Giovanni Camussi ◽  
Paolo Cavallo Perin ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Expression ◽  
Slit Diaphragm ◽  
Peroxisome Proliferator ◽  
Glomerular Permeability ◽  
Receptor System ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Mrna And Protein Expression

Increased glomerular permeability to proteins is a characteristic feature of diabetic nephropathy (DN). The slit diaphragm is the major restriction site to protein filtration, and the loss of nephrin, a key component of the slit diaphragm, has been demonstrated in both human and experimental DN. Both systemic and glomerular hypertension are believed to be important in the pathogenesis of DN. Human immortalized podocytes were subjected to repeated stretch-relaxation cycles by mechanical deformation with the use of a stress unit (10% elongation, 60 cycles/min) in the presence or absence of candesartan (1 μM), PD-123319 (1 μM), and rosiglitazone (0.1 μM). Nephrin mRNA and protein expression were assessed using quantitative real-time PCR, immunoblotting, and immunofluorescence, and the protein expression of AT1 receptor and angiotensin II secretion were evaluated. Exposure to stretch induced a significant ∼50% decrease in both nephrin mRNA and protein expression. This effect was mediated by an angiotensin II-AT1 mechanism. Indeed, podocyte stretching induced both angiotensin II secretion and AT1 receptor overexpression, podocyte exposure to angiotensin II reduced nephrin protein expression, and both the AT-1 receptor antagonist candesartan and a specific anti-angiotensin II antibody completely abolished stretch-induced nephrin downregulation. Similar to candesartan, the peroxisome proliferator-activated receptor (PPAR)-γ agonist, rosiglitazone, also inhibited stretch-induced nephrin downregulation, suggesting interference with stretch-induced activation of the angiotensin II-AT1 receptor system. Accordingly, rosiglitazone did not alter stretch-induced angiotensin II secretion, but it prevented AT1 upregulation in response to stretch. These results suggest a role for hemodynamic stress in loss of nephrin expression and allude to a role of PPAR-γ agonists in the prevention of this loss.

scholarly journals Peroxisome Proliferator-Activated Receptor-γ(PPAR-γ) Agonists Attenuate the Profibrotic Response Induced by TGF-β1 in Renal Interstitial Fibroblasts

2007 ◽  
Vol 2007 ◽  
pp. 1-7 ◽  
Author(s):  
Weiming Wang ◽  
Feng Liu ◽  
Nan Chen
Keyword(s):  
Protein Expression ◽  
Mrna Expression ◽  
Kidney Diseases ◽  
Smooth Muscle Actin ◽  
Tissue Growth ◽  
Time Dependent ◽  
Peroxisome Proliferator ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ

Background.Studies have shown that peroxisome proliferator-activated receptor-γ(PPAR-γ) agonists could ameliorate renal fibrotic lesions in both diabetic nephropathy and nondiabetic chronic kidney diseases. In order to elucidate the antifibrotic mechanism of PPAR-γagonists, we investigated the effects of PPAR-γactivation on TGF-β1-induced renal interstitial fibroblasts.Methods.In rat renal interstitial fibroblasts (NRK/49F), the mRNA expression of TGF-β1-inducedα-smooth muscle actin (α-SMA), connective tissue growth factor (CTGF), fibronectin (FN) and collagen type III (Col III) were observed by reverse transcriptase-polymerase chain reaction (RT-PCR). The protein expressions of FN and Smads were observed by Western blot.Results.In NRK/49F, TGF-β1 enhanced CTGF, FN and Col III mRNA expression in a dose- and time-dependent manner.α-SMA, CTGF, FN and Col III mRNA and FN protein expression in 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2)-troglitazone- and ciglitazone-pretreated groups, respectively, were significantly decreased compared with the TGF-β1-stimulated group. TGF-β1 (5 ng/mL) enhanced p-Smad2/3 protein expression in a time-dependent manner. Compared with the TGF-β1-stimulated group, p-Smad2/3 protein induced by TGF-β1 in PPAR-γagonists-pretreated groups significantly decreased with no statistical difference amongst the three pretreated groups.Conclusion.PPAR-γagonists could inhibit TGF-β1-induced renal fibroblast activation, CTGF expression and ECM synthesis through abrogating the TGF-β1/Smads signaling pathway.

The effect of high glucose and PPAR-γ agonists on PPAR-γ expression and function in HK-2 cells

2004 ◽  
Vol 287 (3) ◽  
pp. F528-F534 ◽  
Author(s):  
U. Panchapakesan ◽  
C. A. Pollock ◽  
X. M. Chen
Keyword(s):  
Cell Growth ◽  
High Glucose ◽  
Transforming Growth Factor ◽  
Human Kidney ◽  
Transforming Growth Factor Β ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Monocyte Chemoattractant Protein 1 ◽  
Ppar Γ ◽  
Proximal Tubular

Peroxisome proliferator-activated receptor-γ (PPAR-γ) are ligand-activated transcription factors that regulate cell growth, inflammation, lipid metabolism, and insulin sensitivity. PPAR-γ in the human kidney has been described. However, the role of PPAR-γ in proximal tubular cells with respect to cell growth and inflammation in diabetic nephropathy is largely unknown. We evaluated the effect of high (30 mM) d-glucose, thiazolidinedione pioglitazone (10 μM), and the selective PPAR-γ agonist L-805645 (8 μM) on PPAR-γ expression, growth, and inflammatory parameters in the proximal tubular model of HK-2 cells. PPAR-γ was present in HK-2 cells and upregulated with 30 mM d-glucose to 177 ± 31.2% of control ( P < 0.05). PPAR-γ activation was induced by pioglitazone to a similar level to that observed by exposure to high glucose but maximally induced by the selective agonist L-805645. However, L-805645 reduced cell viability in both 5 and 30 mM d-glucose to 73.8 ± 3.1 and 77.6 ± 1.4% of control (both P < 0.0001). In parallel, thymidine incorporation was reduced with L-805645 in both 5 and 30 mM d-glucose to 33.3 ± 3.4 and 37.9 ± 2.2%, respectively (both P < 0.0001). Flow cytometry demonstrated increased apoptosis and G1 phase arrest in association with an increase in p21cip1/waf1 in cells exposed to L-805645. Exposure to 30 mM d-glucose did not significantly change AP-1 promoter activity (89.0 ± 5.5% of control); however, the addition of L-805645 significantly reduced it to 62.2 ± 2.7% of control ( P < 0.0001). Thirty nanomolar d-glucose induced transforming growth factor-β1 to 137.7 ± 16.9% of control ( P < 0.05), and L-805645 was able to suppress this to 68.7 ± 5.7% of control ( P < 0.01 vs. d-glucose). Exposure to 30 mM d-glucose reduced monocyte chemoattractant protein 1 levels to 78.6 ± 7.1% ( P < 0.05) of control, with the reduction more marked in the presence of either pioglitazone ( P < 0.01) or L-805645 ( P < 0.01). In summary, high glucose upregulates PPAR-γ and when significantly induced demonstrates anti-proliferative and anti-inflammatory effects.

scholarly journals Curcumin promotes oligodendrocyte differentiation and their protection against TNF-α through the activation of the nuclear receptor PPAR-γ

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Antonietta Bernardo ◽  
Cristina Plumitallo ◽  
Chiara De Nuccio ◽  
Sergio Visentin ◽  
Luisa Minghetti
Keyword(s):  
Therapeutic Potential ◽  
Core Protein ◽  
Curcuma Longa ◽  
Demyelinating Diseases ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Inflammatory Conditions ◽  
Ppar Γ ◽  
Tnf Α ◽  
Anti Inflammatory

AbstractCurcumin is a compound found in the rhizome of Curcuma longa (turmeric) with a large repertoire of pharmacological properties, including anti-inflammatory and neuroprotective activities. The current study aims to assess the effects of this natural compound on oligodendrocyte progenitor (OP) differentiation, particularly in inflammatory conditions. We found that curcumin can promote the differentiation of OPs and to counteract the maturation arrest of OPs induced by TNF-α by a mechanism involving PPAR-γ (peroxisome proliferator activated receptor), a ligand-activated transcription factor with neuroprotective and anti-inflammatory capabilities. Furthermore, curcumin induces the phosphorylation of the protein kinase ERK1/2 known to regulate the transition from OPs to immature oligodendrocytes (OLs), by a mechanism only partially dependent on PPAR-γ. Curcumin is also able to raise the levels of the co-factor PGC1-α and of the cytochrome c oxidase core protein COX1, even when OPs are exposed to TNF-α, through a PPAR-γ-mediated mechanism, in line with the known ability of PPAR-γ to promote mitochondrial integrity and functions, which are crucial for OL differentiation to occur. Altogether, this study provides evidence for a further mechanism of action of curcumin besides its well-known anti-inflammatory properties and supports the suggested therapeutic potential of this nutraceutical in demyelinating diseases.

scholarly journals Andrographis paniculata and Its Main Bioactive Ingredient Andrographolide Decrease Alcohol Drinking and Seeking in Rats Through Activation of Nuclear PPARγ Pathway

2021 ◽  
Author(s):  
Serena Stopponi ◽  
Yannick Fotio ◽  
Carlo Cifani ◽  
Hongwu Li ◽  
Carolina L Haass-Koffler ◽  
...  
Keyword(s):  
Oral Administration ◽  
Alcohol Drinking ◽  
Andrographis Paniculata ◽  
Peroxisome Proliferator ◽  
Herbaceous Plant ◽  
Dependent Manner ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Treatment Administration ◽  
Dried Extract

Abstract Background and aims Andrographis paniculata is an annual herbaceous plant which belongs to the Acanthaceae family. Extracts from this plant have shown hepatoprotective, anti-inflammatory and antidiabetic properties, at least in part, through activation of the nuclear receptor Peroxisome Proliferator-Activated Receptor-gamma (PPAR γ). Recent evidence has demonstrated that activation of PPARγ reduces alcohol drinking and seeking in Marchigian Sardinian (msP) alcohol-preferring rats. Methods The present study evaluated whether A. paniculata reduces alcohol drinking and relapse in msP rats by activating PPARγ. Results Oral administration of an A. paniculata dried extract (0, 15, 150 mg/kg) lowered voluntary alcohol consumption in a dose-dependent manner and achieved ~65% reduction at the dose of 450 mg/kg. Water and food consumption were not affected by the treatment. Administration of Andrographolide (5 and 10 mg/kg), the main active component of A. paniculata, also reduced alcohol drinking. This effect was suppressed by the selective PPARγ antagonist GW9662. Subsequently, we showed that oral administration of A. paniculata (0, 150, 450 mg/kg) prevented yohimbine- but not cues-induced reinstatement of alcohol seeking. Conclusions Results point to A. paniculata-mediated PPARγactivation as a possible therapeutic strategy to treat alcohol use disorder.

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