1211 Peroxisome proliferator-activated receptor Gamma responsible for TGFβ-induced epithelial mesenchymal transition (EMT) and tumor invasion of NSCLC cells (H460)

2009 ◽  
Vol 7 (2) ◽  
pp. 124 ◽  
Author(s):  
L.C. Lin ◽  
S.L. Hsu ◽  
C.L. Wu ◽  
W.C. Liu ◽  
H.T. Chiu ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition

scholarly journals Fenofibrate Improved Interstitial Fibrosis of Renal Allograft through Inhibited Epithelial-Mesenchymal Transition Induced by Oxidative Stress

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Yishu Wang ◽  
Lei Pang ◽  
Yanghe Zhang ◽  
Jiahui Lin ◽  
Honglan Zhou
Keyword(s):  
Oxidative Stress ◽  
Rat Model ◽  
Renal Allograft ◽  
Epithelial Mesenchymal Transition ◽  
Interstitial Fibrosis ◽  
Peroxisome Proliferator ◽  
Tubular Atrophy ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
Stage Renal Disease

The best treatment for end-stage renal disease is renal transplantation. However, it is often difficult to maintain a renal allograft healthy for a long time following transplantation. Interstitial fibrosis and tubular atrophy (IF/TA) are significant histopathologic characteristics of a compromised renal allograft. There is no effective therapy to improve renal allograft function once IF/TA sets in. Although there are many underlying factors that can induce IF/TA, the pathogenesis of IF/TA has not been fully elucidated. It has been found that epithelial-mesenchymal transition (EMT) significantly contributes to the development of IF/TA. Oxidative stress is one of the main causes that induce EMT in renal allografts. In this study, we have used H2O2 to induce oxidative stress in renal tubular epithelial cells (NRK-52e) of rats. We also pretreated NRK-52e cells with an antioxidant (N-acetyl L-cysteine (NAC)) 1 h prior to the treatment with H2O2. Furthermore, we used fenofibrate (a peroxisome proliferator-activated receptor α agonist) to treat NRK-52e cells and a renal transplant rat model. Our results reveal that oxidative stress induces EMT in NRK-52e cells, and pretreatment with NAC can suppress EMT in these cells. Moreover, fenofibrate suppresses fibrosis by ameliorating oxidative stress-induced EMT in a rat model. Thus, fenofibrate may effectively prevent the development of fibrosis in renal allograft and improve the outcome.

scholarly journals Curcumin Suppresses Intestinal Fibrosis by Inhibition of PPARγ-Mediated Epithelial-Mesenchymal Transition

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Su Xu ◽  
Bin Jiang ◽  
Hui Wang ◽  
Cunsi Shen ◽  
Hao Chen ◽  
...  
Keyword(s):  
Nuclear Translocation ◽  
Epithelial Mesenchymal Transition ◽  
Smooth Muscle Actin ◽  
Peroxisome Proliferator ◽  
Colon Tissue ◽  
Peroxisome Proliferator Activated Receptor ◽  
Smad Pathway ◽  
Mesenchymal Transition ◽  
Intestinal Fibrosis ◽  
E Cadherin

Intestinal fibrotic stricture is a major complication of Crohn’s disease (CD) and epithelial-to-mesenchymal transition (EMT) is considered as an important contributor to the formation of intestinal fibrosis by increasing extracellular matrix (ECM) proteins. Curcumin, a compound derived from rhizomes ofCurcuma, has been demonstrated with a potent antifibrotic effect. However, its effect on intestinal fibrosis and the potential mechanism is not completely understood. Here we found that curcumin pretreatment significantly represses TGF-β1-induced Smad pathway and decreases its downstreamα-smooth muscle actin (α-SMA) gene expression in intestinal epithelial cells (IEC-6); in contrast, curcumin increases expression of E-cadherin and peroxisome proliferator-activated receptorγ(PPARγ) in IEC-6. Moreover, curcumin promotes nuclear translocation of PPARγand the inhibitory effect of curcumin on EMT could be reversed by PPARγantagonist GW9662. Consistently, in the rat model of intestinal fibrosis induced by 2,4,5-trinitrobenzene sulphonic acid (TNBS), oral curcumin attenuates intestinal fibrosis by increasing the expression of PPARγand E-cadherin and decreasing the expression ofα-SMA, FN, and CTGF in colon tissue. Collectively, these results indicated that curcumin is able to prevent EMT progress in intestinal fibrosis by PPARγ-mediated repression of TGF-β1/Smad pathway.

scholarly journals PGC-1α Suppresses the Activation of TGF-β/Smad Signaling via Targeting TGFβRI Downregulation by let-7b/c Upregulation

2019 ◽  
Vol 20 (20) ◽  
pp. 5084 ◽  
Author(s):  
Hoon-In Choi ◽  
Jung Sun Park ◽  
Dong-Hyun Kim ◽  
Chang Seong Kim ◽  
Eun Hui Bae ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Epithelial Mesenchymal Transition ◽  
Kidney Diseases ◽  
Peroxisome Proliferator ◽  
Major Pathway ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
Smad Signaling ◽  
Smad Signaling Pathway ◽  
Signaling Activation

TGF-β/Smad signaling is a major pathway in progressive fibrotic processes, and further studies on the molecular mechanisms of TGF-β/Smad signaling are still needed for their therapeutic targeting. Recently, peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) was shown to improve renal fibrosis, making it an attractive target for chronic kidney diseases (CKDs). Here, we show the mechanism by which PGC-1α regulates the TGF-β/Smad signaling pathway using HK-2 cell lines stably overexpressing empty vector (mock cells) or human PGC1α (PGC1α cells). Stable PGC-1α overexpression negatively regulated the expression of TGF-β-induced epithelial-mesenchymal transition (EMT) markers (fibronectin, E-cadherin, vimentin, and α-SMA) and EMT-related transcription factors (Snail and Slug) compared to mock cells, inhibiting fibrotic progression. Interestingly, among molecules upstream of Smad2/3 activation, the gene expression of only TGFβRI, but not TGFβRII, was downregulated in PGC-1α cells. In addition, the downregulation of TGFβRI by PGC-1α was associated with the upregulation of let-7b/c, miRNA for which the 3′ untranslated region (UTR) of TGFβRI contains a binding site. In conclusion, PGC-1α suppresses TGF-β/Smad signaling activation via targeting TGFβRI downregulation by let-7b/c upregulation.

scholarly journals PPAR-gamma induced AKT3 expression increases levels of mitochondrial biogenesis driving prostate cancer

Oncogene ◽  
2021 ◽  
Vol 40 (13) ◽  
pp. 2355-2366
Author(s):  
Laura C. A. Galbraith ◽  
Ernest Mui ◽  
Colin Nixon ◽  
Ann Hedley ◽  
David Strachan ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mitochondrial Biogenesis ◽  
Nuclear Export ◽  
Epithelial To Mesenchymal Transition ◽  
Ppar Gamma ◽  
Peroxisome Proliferator ◽  
Serine Threonine Kinase ◽  
Peroxisome Proliferator Activated Receptor ◽  
Mesenchymal Transition ◽  
And Function

AbstractPeroxisome Proliferator-Activated Receptor Gamma (PPARG) is one of the three members of the PPAR family of transcription factors. Besides its roles in adipocyte differentiation and lipid metabolism, we recently demonstrated an association between PPARG and metastasis in prostate cancer. In this study a functional effect of PPARG on AKT serine/threonine kinase 3 (AKT3), which ultimately results in a more aggressive disease phenotype was identified. AKT3 has previously been shown to regulate PPARG co-activator 1 alpha (PGC1α) localisation and function through its action on chromosome maintenance region 1 (CRM1). AKT3 promotes PGC1α localisation to the nucleus through its inhibitory effects on CRM1, a known nuclear export protein. Collectively our results demonstrate how PPARG over-expression drives an increase in AKT3 levels, which in turn has the downstream effect of increasing PGC1α localisation within the nucleus, driving mitochondrial biogenesis. Furthermore, this increase in mitochondrial mass provides higher energetic output in the form of elevated ATP levels which may fuel the progression of the tumour cell through epithelial to mesenchymal transition (EMT) and ultimately metastasis.

scholarly journals Integrin β4 as a Potential Diagnostic and Therapeutic Tumor Marker

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1197
Author(s):  
Haoyu Yang ◽  
Zixuan Xu ◽  
Yuqian Peng ◽  
Jiali Wang ◽  
Yang Xiang
Keyword(s):  
Signal Transduction ◽  
Tumor Marker ◽  
Tumor Invasion ◽  
Epithelial Mesenchymal Transition ◽  
Vital Role ◽  
Structure And Function ◽  
Mesenchymal Transition ◽  
Tumor Tissues ◽  
Integrin Β4 ◽  
And Function

Integrin β4 (ITGβ4) is a class of transmembrane adhesion molecules composed of hemidesmosomes (HDs). Its unique long intracellular domain provides intricate signal transduction functions. These signal transduction effects are especially prominent in tumors. Many recent studies have shown that integrin β4 is differentially expressed in various tumors, and it plays a vital role in tumor invasion, proliferation, epithelial–mesenchymal transition, and angiogenesis. Therefore, we categorize the research related to integrin β4, starting from its structure and function in tumor tissues, and provide a basic description. Based on its structure and function, we believe that integrin β4 can be used as a tumor marker. In clinical practice, it is described as a diagnostic marker for the targeted treatment of cancer and will be helpful in the clinical diagnosis and treatment of tumors.

scholarly journals Mechanophenotyping of 3D multicellular clusters using displacement arrays of rendered tractions

2020 ◽  
Vol 117 (11) ◽  
pp. 5655-5663 ◽  
Author(s):  
Susan E. Leggett ◽  
Mohak Patel ◽  
Thomas M. Valentin ◽  
Lena Gamboa ◽  
Amanda S. Khoo ◽  
...  
Keyword(s):  
Tumor Invasion ◽  
Wound Repair ◽  
Epithelial Mesenchymal Transition ◽  
Ex Vivo ◽  
Three Dimensional ◽  
Human Patient ◽  
Mesenchymal Transition ◽  
Successive Loss ◽  
Surrounding Extracellular Matrix

Epithelial tissues mechanically deform the surrounding extracellular matrix during embryonic development, wound repair, and tumor invasion. Ex vivo measurements of such multicellular tractions within three-dimensional (3D) biomaterials could elucidate collective dissemination during disease progression and enable preclinical testing of targeted antimigration therapies. However, past 3D traction measurements have been low throughput due to the challenges of imaging and analyzing information-rich 3D material deformations. Here, we demonstrate a method to profile multicellular clusters in a 96-well-plate format based on spatially heterogeneous contractile, protrusive, and circumferential tractions. As a case study, we profile multicellular clusters across varying states of the epithelial–mesenchymal transition, revealing a successive loss of protrusive and circumferential tractions, as well as the formation of localized contractile tractions with elongated cluster morphologies. These cluster phenotypes were biochemically perturbed by using drugs, biasing toward traction signatures of different epithelial or mesenchymal states. This higher-throughput analysis is promising to systematically interrogate and perturb aberrant mechanobiology, which could be utilized with human-patient samples to guide personalized therapies.

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