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mTOR AND Smad

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https://www.readbyqxmd.com/read/28524854/a-smad3-pten-regulatory-loop-controls-proliferation-and-apoptotic-responses-to-tgf-%C3%AE-in-mouse-endometrium
#1
Nuria Eritja, Isidre Felip, Mari Alba Dosil, Lucia Vigezzi, Cristina Mirantes, Andree Yeramian, Raúl Navaridas, Maria Santacana, David Llobet-Navas, Akihiko Yoshimura, Masatoshi Nomura, Mario Encinas, Xavier Matias-Guiu, Xavi Dolcet
The TGF-β/Smad and the PI3K/AKT signaling pathways are important regulators of proliferation and apoptosis, and their alterations lead to cancer development. TGF-β acts as a tumor suppressor in premalignant cells, but it is a tumor promoter for cancerous cells. Such dichotomous actions are dictated by different cellular contexts. Here, we have unveiled a PTEN-Smad3 regulatory loop that provides a new insight in the complex cross talk between TGF-β/Smad and PI3K/AKT signaling pathways. We demonstrate that TGF-β triggers apoptosis of wild-type polarized endometrial epithelial cells by a Smad3-dependent activation of PTEN transcription, which results in the inhibition of PI3K/AKT signaling pathway...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28396841/ubiquitin-ligase-smurf1-functions-as-a-prognostic-marker-and-promotes-growth-and-metastasis-of-clear-cell-renal-cell-carcinoma
#2
Mang Ke, Licai Mo, Weilin Li, Xianjun Zhang, Feiping Li, Hongyuan Yu
Smad ubiquitin regulatory factor 1 (SMURF1), a recently identified E3 ubiquitin ligase, targets substrate proteins for ubiquitination and proteasomal degradation. Previous studies have reported that SMURF1 also functions as an oncogene in human cancers. However, the clinical value of SMURF1 and its role in clear cell renal cell carcinoma (ccRCC) are unknown. SMURF1 expression was analyzed in 100 cases of ccRCC and matched tumor-adjacent specimens. SMURF1 was prominently overexpressed in ccRCC specimens compared with tumor-adjacent specimens...
April 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28378496/c-reactive-protein-and-ageing
#3
Ying Tang, Erik Fung, Anping Xu, Hui-Yao Lan
Increasing evidence shows that C-reactive protein (CRP) is not only an inflammatory biomarker but also an important risk factor associated with ageing-related diseases including cardiovascular disease, hypertension, diabetes mellitus, and kidney disease. Recent studies have demonstrated that CRP is pathogenic in a number of diseases including hypertensive cardiovascular and kidney complications, diabetic nephropathy, and acute and chronic kidney diseases. It is well known that CRP binds its receptor, CD32/CD64, to induce the process of inflammation by activating the NF-κB signalling pathway...
April 4, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28374926/role-of-endothelial-to-mesenchymal-transition-induced-by-tgf-%C3%AE-1-in-transplant-kidney-interstitial-fibrosis
#4
Zijie Wang, Zhijian Han, Jun Tao, Jun Wang, Xuzhong Liu, Wanli Zhou, Zhen Xu, Chunchun Zhao, Zengjun Wang, Ruoyun Tan, Min Gu
Chronic allograft dysfunction (CAD) induced by kidney interstitial fibrosis is the main cause of allograft failure in kidney transplantation. Endothelial-to-mesenchymal transition (EndMT) may play an important role in kidney fibrosis. We, therefore, undertook this study to characterize the functions and potential mechanism of EndMT in transplant kidney interstitial fibrosis. Proteins and mRNAs associated with EndMT were examined in human umbilical vein endothelial cells (HUVECs) treated with transforming growth factor-beta1 (TGF-β1) at different doses or at different intervals with western blotting, qRT-PCR and ELISA assays...
April 4, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28301572/far-infrared-suppresses-skin-photoaging-in-ultraviolet-b-exposed-fibroblasts-and-hairless-mice
#5
Hui-Wen Chiu, Cheng-Hsien Chen, Yi-Jie Chen, Yung-Ho Hsu
Ultraviolet (UV) induces skin photoaging, which is characterized by thickening, wrinkling, pigmentation, and dryness. Collagen, which is one of the main building blocks of human skin, is regulated by collagen synthesis and collagen breakdown. Autophagy was found to block the epidermal hyperproliferative response to UVB and may play a crucial role in preventing skin photoaging. In the present study, we investigated whether far-infrared (FIR) therapy can inhibit skin photoaging via UVB irradiation in NIH 3T3 mouse embryonic fibroblasts and SKH-1 hairless mice...
2017: PloS One
https://www.readbyqxmd.com/read/28288846/pleiotropic-fty720-is-a-specific-and-potent-therapy-for-hypertrophic-scars
#6
Fen Shi, Xiaoling Cao, Zhicheng Hu, Da Ma, Dong Guo, Jian Zhang, Changlin Zhang, Peng Liu, Shanqiang Qu, Jiayuan Zhu, Wuguo Deng, Bing Tang
Hypertrophic scarring (HS) is a fibrotic skin condition characterized by aberrant fibroblast phenotypes and excessive deposition of extracellular matrix components. 2-Amino-2-[2-(4-octylphenyl)]-1, 3-propanediol hydrochloride (FTY720), an immunomodulator approved for treating multiple sclerosis, is reported to attenuate fibrosis in multiple disease models. Here we found that FTY720 could significantly attenuate the proliferation and fibrosis in HS fibroblasts (HSFs) and in an animal HS model. Upon treating HSFs or normal dermal fibroblasts with FTY720 at different concentrations for different time periods, we found that FTY720 presented a pleiotropic effect specifically on HSFs but not NFs, including reducing cell viability, arresting cell cycle progression at the G0/G1 phase, promoting apoptosis, inhibiting migration and contraction, and suppressing the expressions of α-smooth muscle actin, collagen I, and collagen III...
March 10, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28078713/the-novel-mtor-complex-1-2-inhibitor-p529-inhibits-human-lung-myofibroblast-differentiation
#7
Keith T Ferguson, Elizabeth E Torr, Ksenija Bernau, Jonathan Leet, David Sherris, Nathan Sandbo
Idiopathic pulmonary fibrosis is a progressive and deadly disorder with very few therapeutic options. Palomid 529 (8-(1-hydroxyethyl)-2-methoxy-3-(4-methoxybenzyloxy)-benzo[c]chromen-6-one; P529) is a novel dual inhibitor of mechanistic target of rapamycin complex 1/2 (mTORC1/2). In these studies, we investigated the effect of P529 on TGF-β-dependent signaling and myofibroblast differentiation. TGF-β-induced phosphorylation of the mTORC1 targets, p70 S6 kinase 1 (S6K1), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1), were both dose dependently inhibited by P529 in human lung fibroblasts with maximal inhibition occurring between 10 and 20 μM...
January 11, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27898339/dietary-phytochemicals-for-possible-preventive-and-therapeutic-option-of-uterine-fibroids-signaling-pathways-as-target
#8
REVIEW
Md Soriful Islam, James H Segars, Mario Castellucci, Pasquapina Ciarmela
A growing interest has emerged on dietary phytochemicals to control diverse pathological conditions. Unfortunately, dietary phytochemical research in uterine fibroids is still under construction. Uterine fibroids/leiomyomas are benign tumors developing from the myometrium of the uterus in premenopausal women. They may occur in more than 70% of women, and approximately 25% of women show clinically significant symptoms. These include heavy and prolonged menstrual bleeding, pelvic pressure (urinary frequency, incontinence, and difficulty with urination), pelvic pain, pelvic mass, infertility, and reproductive dysfunction...
February 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/27881603/a-protective-role-of-il-37-in-cancer-a-new-hope-for-cancer-patients
#9
REVIEW
Ayoub Abulkhir, Suzanne Samarani, Devendra Amre, Michel Duval, Elie Haddad, Daniel Sinnett, Jean-Marie Leclerc, Caroline Diorio, Ali Ahmad
IL-37 is a cytokine belonging to the IL-1 family. Although discovered in silico in 2000, significant advances in the understanding of its biology were made only in recent years. It is a member of the family with potent anti-inflammatory and immunosuppressive properties. It is produced as a precursor without a classic signal peptide. The precursor is cleaved into mature form in the cytoplasm by caspase-1. A small fraction of the cleaved IL-37 binds SMAD-3, translocates to the nucleus, and suppresses transcription of several proinflammatory genes...
November 23, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27808010/role-of-neuroinflammation-and-latent-transcription-factors-in-pathogenesis-of-parkinson-s-disease
#10
Rishi Pal, Prafulla Chandra Tiwari, Rajendra Nath, Kamlesh Kumar Pant
Parkinson's disease (PD) the second most common age-associated progressive neurodegenerative disorder is characterized by loss of dopaminergic neurons, cytoplasmic inclusions of aggregated proteins (Lewy bodies), and neuroinflammation. The inflammation of neurons causes release of various inflammatory mediators (IFNs, EGF, IL5, IL6, HGF, LIF and BMP2). The hallmarks of neuroinflammation are the presence of activated microglia and reactive astrocytes in the parenchyma of the CNS and increased production of cytokines, chemokines, prostaglandins, complement cascade proteins, and reactive oxygen and nitrogen species (ROS/RNS) which in some cases can result in disruption of the blood brain barrier and direct participation of the adaptive immune system...
December 2016: Neurological Research
https://www.readbyqxmd.com/read/27756878/plumbagin-protects-liver-against-fulminant-hepatic-failure-and-chronic-liver-fibrosis-via-inhibiting-inflammation-and-collagen-production
#11
Huafeng Wang, Huan Zhang, Yuqing Zhang, Dan Wang, Xixi Cheng, Fengrui Yang, Qi Zhang, Zhenyi Xue, Yan Li, Lijuan Zhang, Luhong Yang, Guolin Miao, Daiqing Li, Zhiyu Guan, Yurong Da, Zhi Yao, Fei Gao, Liang Qiao, Li Kong, Rongxin Zhang
Plumbagin is a quinonoid constituent extracted from Plumbago genus, and it exhibits diverse pharmacological effects. This study thoroughly investigated the effects of plumbagin on thioacetamide-induced acute and chronic liver injury. Results shown that plumbagin increased survival rate, reduced liver congestion and inflammation, and decreased macrophages and neutrophils in the fulminant hepatic failure model, and remarkably diminished liver fibrosis and inflammation in the chronic liver injury model. Furthermore, plumbagin significantly suppress the HSCs/myofibroblasts activation by reduced expression of markers α-SMA and COL-1/3, and reduced macrophage in liver...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27568833/mechanistic-insight-of-diabetic-nephropathy-and-its-pharmacotherapeutic-targets-an-update
#12
REVIEW
Niloy Bhattacharjee, Sujata Barma, Nandita Konwar, Saikat Dewanjee, Prasenjit Manna
Diabetic nephropathy (DN), a chronic complication of diabetes, is charecterized by glomerular hypertrophy, proteinuria, decreased glomerular filtration, and renal fibrosis resulting in the loss of renal function. Although the exact cause of DN remains unclear, several mechanisms have been postulated, such as hyperglycemia-induced renal hyper filtration and renal injury, AGEs-induced increased oxidative stress, activated PKC-induced increased production of cytokines, chemokines, and different inflammatory and apoptotic signals...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27551760/the-inhibition-of-macrophage-foam-cell-formation-by-tetrahydroxystilbene-glucoside-is-driven-by-suppressing-vimentin-cytoskeleton
#13
Wenjuan Yao, Lei Huang, Qinju Sun, Lifeng Yang, Lian Tang, Guoliang Meng, Xiaole Xu, Wei Zhang
Macrophage foam cell formation triggered by oxLDL is an important event that occurs during the development of atherosclerosis. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (TSG) exhibits significant anti-atherosclerotic activity. Herein we used U937 cells induced by PMA and oxLDL in vitro to investigate the inhibitory effects of TSG on U937 differentiation and macrophage foam cell formation. TSG pretreatment markedly inhibited cell differentiation induced by PMA, macrophage apoptosis and foam cell formation induced by oxLDL...
October 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27340276/molecular-pathways-cachexia-signaling-a-targeted-approach-to-cancer-treatment
#14
Yuji Miyamoto, Diana L Hanna, Wu Zhang, Hideo Baba, Heinz-Josef Lenz
Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival...
August 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27239444/mtor-inhibition-by-rapamycin-increases-ceramide-synthesis-by-promoting-transforming-growth-factor-%C3%AE-1-smad-signaling-in-the-skin
#15
Takumi Yamane, Aimi Muramatsu, Sawako Yoshino, Sho Matsui, Mari Shimura, Yoshimasa Tsujii, Ken Iwatsuki, Kazuo Kobayashi-Hattori, Yuichi Oishi
Although mammalian target of rapamycin (mTOR) mediates a wide variety of biological functions, little information is available on the effect of mTOR on the functions of skin cells. In this study, we investigated effects of mTOR inhibition by rapamycin on ceramide synthesis in the skin of rats and human keratinocytes and its regulatory mechanisms. The phosphorylation of p70 S6 kinase, which indicates mTOR activation, was induced in the skin of rats fed a high-fat diet, but this abnormality was reversed by supplementation with rapamycin...
April 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/27114559/gdf-15-enhances-intracellular-ca2-by-increasing-cav1-3-expression-in-rat-cerebellar-granule-neurons
#16
Jun-Mei Lu, Chang-Ying Wang, Changlong Hu, Yan-Jia Fang, Yan-Ai Mei
GDF-15 (growth/differentiation factor 15) is a novel member of the TGF (transforming growth factor)-β superfamily that has critical roles in the central and peripheral nervous systems. We reported previously that GDF-15 increased delayed rectifier outward K(+) currents and Kv2.1 α subunit expression through TβRII (TGF-β receptor II) to activate Src kinase and Akt/mTOR (mammalian target of rapamycin) signalling in rat CGNs (cerebellar granule neurons). In the present study, we found that treatment of CGNs with GDF-15 for 24 h increased the intracellular Ca(2+) concentration ([Ca(2+)]i) in response to membrane depolarization, as determined by Ca(2+) imaging...
July 1, 2016: Biochemical Journal
https://www.readbyqxmd.com/read/27100493/the-pi3k-akt-pathway-in-the-pathogenesis-of-prostate-cancer
#17
Huixing Chen, Lan Zhou, Xiaorong Wu, Rongbing Li, Jiling Wen, Jianjun Sha, Xiaofei Wen
Despite recent advances in our understanding of the biological behavior of prostate cancer (PCa), PCa is becoming the most common malignancy in men worldwide. The phosphatidylinositol 3-kinase (PI3K)/AKT pathway has been implicated in prostate carcinogenesis. Inflammatory cytokines (CCR9, IL-6, and TLR3) regulate PI3K/AKT signaling during apoptosis of PCa cells, and PI3K/AKT signaling participates with androgen-, 1alpha,25(OH)2-vitamin D3-, and prostaglandin-associated mechanisms and is regulated by ErbB, EGFR, and the HER family during cell growth...
2016: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/26749690/features-of-intestinal-lesions-in-the-clinical-course-of-inflammatory-bowel-diseases
#18
REVIEW
Antonella Vetuschi, Giovanni Latella, Simona Pompili, Eugenio Gaudio, Roberta Sferra
Inflammatory bowel diseases (IBD), including ulcerative colitis (UC) and Crohn's disease (CD), are chronic, progressive and relapsing inflammatory disorders of unknown etiology. UC is characterized by inflammation of the large bowel mucosa and submucosa, whereas in CD inflammation is transmural and may involve various sites of the gastrointestinal tract. Superficial mucosal lesions are most prone to heal, whereas deep ulcers or transmural fissures may heal with more difficulty and may be followed by the development of fibrosis and strictures requiring surgery...
2014: Italian Journal of Anatomy and Embryology, Archivio Italiano di Anatomia Ed Embriologia
https://www.readbyqxmd.com/read/26709801/new-genomic-landscapes-and-therapeutic-targets-for-biliary-tract-cancers
#19
REVIEW
Michele Simbolo, Matteo Fassan, Andrea Mafficini, Rita T Lawlor, Andrea Ruzzenente, Aldo Scarpa
Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations...
January 1, 2016: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/26689334/transcriptome-analysis-of-the-molting-gland-y-organ-from-the-blackback-land-crab-gecarcinus-lateralis
#20
Sunetra Das, Natalie L Pitts, Megan R Mudron, David S Durica, Donald L Mykles
In decapod crustaceans, arthropod steroid hormones or ecdysteroids regulate molting. These hormones are synthesized and released from a pair of molting glands called the Y-organs (YO). Cyclic nucleotide, mTOR, and TGFβ/Smad signaling pathways mediate molt cycle-dependent phase transitions in the YO. To further identify the genes involved in the regulation of molting, a YO transcriptome was generated from three biological replicates of intermolt blackback land crab, Gecarcinus lateralis. Illumina sequencing of cDNA libraries generated 227,811,829 100-base pair (bp) paired-end reads; following trimming, 90% of the reads were used for further analyses...
March 2016: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
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