scholarly journals Fluorofenidone attenuates paraquat‑induced pulmonary fibrosis by regulating the PI3K/Akt/mTOR signaling pathway and autophagy

2021 ◽  
Vol 23 (6) ◽  
Author(s):  
Feiya Jiang ◽  
Sha Li ◽  
Yu Jiang ◽  
Zhuo Chen ◽  
Tongtong Wang ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

scholarly journals Activated mTORC1-SIRT6 Mediates Myofibroblast Differentiation and Idiopathic Pulmonary Fibrosis

2021 ◽  
Author(s):  
Ji Zhang ◽  
Yi Hu ◽  
Huiping Huang ◽  
Qun Liu ◽  
Yang Du ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Signalling Pathway ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Dependent Manner ◽  
Mtor Signaling Pathway ◽  
Mtorc1 Pathway ◽  
Tgf Β1

Abstract BackgroundIdiopathic pulmonary fibrosis (IPF) is characterised by accumulation of myofibroblasts and deposition of extracellular matrix proteins. Fibroblast-to-myofibroblast transdifferentiation and myofibroblast hyperproliferation plays a major role in pulmonary fibrosis. Moreover, mTOR signaling pathway and SIRT6 play a critical role in pulmonary fibrosis. However, the mechanisms whether SIRT6 affect the myofibroblasts differentiation during IPF remain unclear.MethodWe investigated myofibroblast differentiation using a bleomycin-induced mouse pulmonary fibrosis model and TGF-b1 induced human fetal lung fibroblasts (MRC5) in vitro. We used both SIRT6 siRNA and rapamycin to study the role of SIRT6 and mTOR signaling pathway in the normal human lung fibroblasts and the myofibroblasts from human IPF lungs.ResultsOur data show that high level of SIRT6 was detected in IPF samples, and SIRT6 was significantly upregulated by TGF-β1 in a time and concentration-dependent manner. SIRT6 expression and activation of mTORC1 signalling pathway were upregulated in fibrotic lung tissues and primary lung fibroblasts isolated from patients with IPF and bleomycin-challenged mice. Furthermore, rapamycin treatment inhibited mTORC1 pathway activity and SIRT6 protein expression. SIRT6 SiRNA failed to mediate the activity of mTORC1 pathway and autophagy induction. However, SIRT6 knockdown could promote TGF-b1 induced pro-fibrotic cytokines.ConclusionActivated mTORC1 signalling pathway regulated SIRT6 overexpression. Deficiency of SIRT6 mediated myofibroblasts differentiation through induced pro-fibrotic cytokines production in the present of TGF-β1. The study indicated that manipulations of SIRT6 expression may provide a new therapeutic strategy to prevent and reverse the progression of pulmonary fibrosis.

scholarly journals mTORC1 Signaling Pathway Mediated SIRT6 Overexpression in TGF-β1-Induced Pulmonary Fibrosis

2021 ◽  
Author(s):  
Ji Zhang ◽  
Yi Hu ◽  
Huiping Huang ◽  
Qun Liu ◽  
Yang Du ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Signaling Pathway ◽  
Critical Role ◽  
Mtor Signaling ◽  
Lung Fibroblasts ◽  
Dependent Manner ◽  
Mtor Signaling Pathway ◽  
Mtorc1 Signaling ◽  
Mtorc1 Pathway ◽  
Tgf Β1

Abstract Fibroblast-to-myofibroblast transdifferentiation and myofibroblast hyperproliferation play a major role in Idiopathic pulmonary fibrosis (IPF). It was also reported that mTOR signaling pathway and SIRT6 have a critical role in pulmonary fibrosis. However, the mechanisms whether mTOR signaling pathway and SIRT6 affect the myofibroblasts differentiation in IPF remain unclear. The results show that SIRT6 is significantly upregulated by TGF-β1 with a time and concentration-dependent manner in MRC5 line and primary lung fibroblasts isolated from IPF patients. SIRT6 protein is also increased in IPF fibrotic lung tissues and bleomycin-challenged mice lung tissues. Also, the activity of mTOR signaling is activated in MRC5 and primary lung fibroblasts. Furthermore, the inhibitor of mTOR, rapamycin treatment significantly suppress mTORC1 pathway activity and SIRT6 protein expression. SIRT6 siRNA failed to mediate the activity of mTORC1 pathway and autophagy induction. Finally, deficiency of SIRT6 could promote TGF-β1 induced pro-fibrotic cytokines. In summary, the study have suggested that SIRT6 is a downstream of mTORC1 signaling pathway in the pulmonary fibrosis caused by TGF-β1-induced. Deficiency of SIRT6 mediated myofibroblasts differentiation through induced pro-fibrotic cytokines production but not induced-autophagy. It was indicated that manipulations of SIRT6 expression may provide a new therapeutic strategy to reverse the progression of pulmonary fibrosis.

UPF1 Impacts on mTOR Signaling Pathway and Autophagy in Endometrioid Endometrial Carcinoma

2020 ◽  
Author(s):  
Minfen Zhang ◽  
Hui Chen ◽  
Ping Qin ◽  
Tonghui Cai ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

2020 ◽  
Vol 27 ◽  
Author(s):  
Naser-Aldin Lashgari ◽  
Nazanin Momeni Roudsari ◽  
Saeideh Momtaz ◽  
Negar Ghanaatian ◽  
Parichehr Kohansal ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Target Of Rapamycin ◽  
In Vivo Studies ◽  
Cochrane Library ◽  
Mtor Signaling Pathway ◽  
Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

Targeting the PI3K/AKT/mTOR Signaling Pathway in Primary Central Nervous System Lymphoma: Current Status and Future Prospects

2020 ◽  
Vol 19 (3) ◽  
pp. 165-173
Author(s):  
Xiaowei Zhang ◽  
Yuanbo Liu
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Signaling Pathway ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Antitumor Effects ◽  
Term Survival

Primary Central Nervous System Lymphoma (PCNSL) is a rare invasive extranodal non- Hodgkin lymphoma, a vast majority of which is Diffuse Large B-Cell Lymphoma (DLBCL). Although high-dose methotrexate-based immunochemotherapy achieves a high remission rate, the risk of relapse and related death remains a crucial obstruction to long-term survival. Novel agents for the treatment of lymphatic malignancies have significantly broadened the horizons of therapeutic options for PCNSL. The PI3K/AKT/mTOR signaling pathway is one of the most important pathways for Bcell malignancy growth and survival. Novel therapies that target key components of this pathway have shown antitumor effects in many B-cell malignancies, including DLBCL. This review will discuss the aberrant status of the PI3K/AKT/mTOR signaling pathways in PCNSL and the application prospects of inhibitors in hopes of providing alternative clinical therapeutic strategies and improving prognosis.

Exploration of the Effect and Mechanism of ShenQi Compound in a Spontaneous Diabetic Rat Model

2019 ◽  
Vol 19 (5) ◽  
pp. 622-631 ◽  
Author(s):  
Ya Liu ◽  
Jian Kang ◽  
Hong Gao ◽  
Xiyu Zhang ◽  
Jun Chao ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Signaling Pathway ◽  
Rat Model ◽  
Mtor Signaling ◽  
Diabetic Rat ◽  
Gene Microarray ◽  
Mtor Signaling Pathway ◽  
Glucose Fluctuation ◽  
Blood Glucose Fluctuation ◽  
Diabetic Rat Model

Background: Type 2 Diabetes Mellitus (T2DM) is a world-wide metabolic disease with no cure from drugs and treatment. In China, The Traditional Chinese Medicine (TCM) herbal formulations have been used to treat T2DM for centuries. Methods: In this study, we proposed a formula called ShenQi Compound (SQC), which has been used in clinical therapeutics in China for several years. We evaluated the effect of SQC in a spontaneous diabetic rat model (GK rats) by detecting a series of blood indicators and performing histological observations. Meanwhile, the gene microarray and RT-qPCR experiments were used to explore the molecular mechanism of SQC treatment. In addition, western medicine, sitagliptin was employed as a comparison. Results: The results indicated that SQC and sitagliptin could effectively improve the serum lipid (blood Total Cholesterol (TC) and blood Triglycerides (TG)), hormone levels (serum insulin (INS), Glucagon (GC) and Glucagon-Like Peptide-1 (GLP-1)), alleviated the inflammatory response (hypersensitive C-Reactive Protein (hsCRP)), blood glucose fluctuation (Mean Blood Glucose (MBG), standard deviation of blood glucose (SDBG) and Largest Amplitude of plasma Glucose Excursions (LAGE)), pancreatic tissue damage and vascular injury for T2DM. Compared with sitagliptin, SQC achieved a better effect on blood glucose fluctuation (p<0.01). Meanwhile, the gene microarray and RT-qPCR experiments indicated that SQC and sitagliptin may improve the T2DM through affecting the biological functions related to apoptosis and circadian rhythm. Moreover, SQC might be able to influence the mTOR signaling pathway by regulating Pik3r1, Ddit4 expression. Conclusion: All these results indicate that SQC is an effective therapeutic drug on T2DM. Notably, SQC presents an obvious blood glucose fluctuation-preventing ability, which might be derived from the regulation of the mTOR signaling pathway.

Homer1a protects against neuronal injury via PI3K/AKT/mTOR signaling pathway

2020 ◽  
Vol 130 (6) ◽  
pp. 621-630 ◽  
Author(s):  
Yuan Wang ◽  
MingMing Zhao ◽  
Lv Shang ◽  
Yanguo Zhang ◽  
Conggang Huang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Neuronal Injury ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway
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