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Pharmacology & Pharmacy
Yue Lu, Haiming Chen, Junhong Zhang, Bin Tang, Hongyu Zhang, Changju Ma, Xiaojuan Tang, Li Li, Jingjing Wu, Jianan Wei, Shaoping Li, Lei Yang, Ling Han, Chuanjian Lu
Summary: The study demonstrated that FZHFZY could inhibit cell proliferation and improve epidermal differentiation in IL-17A/IL-22/IFN-gamma/TNF-alpha-induced HaCaT cells, while alleviating symptoms and regulating epidermal differentiation in a mouse model of imiquimod-induced psoriasis, and inhibiting phosphorylation of the Akt/mTORC1/S6K1 pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Qinqin Peng, Ke Sha, Yingzi Liu, Mengting Chen, San Xu, Hongfu Xie, Zhili Deng, Ji Li
Summary: The study found that angiogenesis was enhanced in both rosacea patients and LL37-induced rosacea-like mice, with inhibition of angiogenesis alleviating rosacea-like features. Activation of mTORC1 in endothelial cells was observed in the lesional skin, and inhibiting mTORC1 decreased angiogenesis and blocked rosacea development. In vitro results showed that inhibiting mTORC1 signaling significantly decreased LL37-induced tube formation of human endothelial cells, suggesting that targeting angiogenesis may be a potential therapy for rosacea.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Gastroenterology & Hepatology
Suyavaran Arumugam, Binghua Li, Sri Lakshmi Tejaswi Boodapati, Michael H. Nathanson, Beicheng Sun, Xinshou Ouyang, Wajahat Z. Mehal
Summary: TGF-beta induces HSC transdifferentiation by releasing mitochondrial DNA and activating the cGAS-STING-IRF3 pathway.
Article
Cell Biology
Jiayang Cai, Zhang Ye, Yuanyuan Hu, Liguo Ye, Lun Gao, Yixuan Wang, Qian Sun, Shiao Tong, Shenqi Zhang, Liquan Wu, Ji'an Yang, Qianxue Chen
Summary: In this study, we found that fatostatin induces ferroptosis in glioblastoma by inhibiting the AKT/mTORC1/GPX4 signaling pathway. Fatostatin also inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. Additionally, we developed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which can penetrate the blood-brain barrier and target GBM.
CELL DEATH & DISEASE
(2023)
Article
Cell Biology
Lilei Peng, Jie Fu, Yitian Chen, Yang Ming, Haiping He, Shan Zeng, Chuanhong Zhong, Ligang Chen
Summary: The current study revealed that SNAI2 is highly expressed in glioma tissues, and its overexpression is associated with poor overall survival in glioma patients. SNAI2 promotes the proliferation of GSCs by inhibiting PHLPP2 and activating the Akt pathway.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Kun Yang, Jie Han, Mayumi Asada, Jennifer G. Gill, Jason Y. Park, Meghana N. Sathe, Jyothsna Gattineni, Tracey Wright, Christian A. Wysocki, M. Teresa de la Morena, Luis A. Garza, Nan Yan
Summary: Inborn errors of nucleic acid metabolism often cause aberrant activation of nucleic acid sensing pathways, leading to autoimmune or autoinflammatory diseases. This study demonstrates the physiological function of SKIV2L in mammals. Skiv2l deficiency disrupts the homeostasis of epidermis and T cells, resulting in skin inflammation and hair abnormality. SKIV2L loss activates the mTORC1 pathway and drives autoinflammatory disease.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Chih-Yao Chung, Kritarth Singh, Vassilios N. Kotiadis, Gabriel E. Valdebenito, Jee Hwan Ahn, Emilie Topley, Joycelyn Tan, William D. Andrews, Benoit Bilanges, Robert D. S. Pitceathly, Gyorgy Szabadkai, Mariia Yuneva, Michael R. Duchen
Summary: Heteroplasmic mtDNA mutations, specifically the m.3243 A > G mutation, lead to activated PI3K-Akt-mTORC1 pathway in cells, and inhibiting this pathway reduces mutant mtDNA load. Pharmacological inhibition of PI3K, Akt, or mTORC1 can potentially benefit people with the consequences of the m.3243 A > G mutation by reducing mutant mtDNA load and improving cellular bioenergetic function.
NATURE COMMUNICATIONS
(2021)
Article
Pharmacology & Pharmacy
Jiahuan Li, Xiaoling Deng, Shuhan Wang, Qianqian Jiang, Keshu Xu
Summary: The study demonstrated that RvD1 effectively reduced liver injury and fibrosis induced by CCl4 in mice by inhibiting pro-fibrotic gene expression and restoring damaged histological architecture. In vitro, RvD1 suppressed LX-2 cell activation and proliferation. Additionally, RvD1 exerted its protective effects by inhibiting autophagy in hepatic stellate cell activation, partly through the AKT/mTOR pathway.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Multidisciplinary Sciences
Yui Kotani, Mami Sumiyoshi, Megumi Sasada, Toshio Watanabe, Satoshi Matsuda
Summary: This study reveals that Arf1 plays an important role in the activation of mTORC1 and cell proliferation in mast cells, but has little impact on degranulation and cytokine secretion. This finding suggests the potential of Arf1 as a therapeutic target for mast cell proliferative disorders.
SCIENTIFIC REPORTS
(2022)
Article
Medicine, Research & Experimental
Yijin Chen, Tong Xu, Mengsha Li, Chuling Li, Yusheng Ma, Guojun Chen, Yili Sun, Hao Zheng, Guangkai Wu, Wangjun Liao, Yulin Liao, Yanmei Chen, Jianping Bin
Summary: Post-translational modification by SUMO is crucial for cell proliferation and can be reversed by SENPs, providing a potential mechanism for cardiac regeneration. Targeting Akt SUMOylation enhances cardiac regeneration, as seen with SENP2 deficiency leading to CM dedifferentiation and proliferation. Loss of SENP2 increases Akt kinase activity, promoting CM proliferation and angiogenesis through Akt pathway activation, contributing to improved cardiac function post-MI.
Article
Cell Biology
Hui Li, Bingxin Guan, Sen Liu, Haiting Liu, Lin Song, Guohao Zhang, Ruinan Zhao, Chengjun Zhou, Peng Gao
Summary: Gastric cancer is a highly heterogeneous disease with poor prognosis. Protein tyrosine phosphatases, specifically PTPN14, play a vital role in gastric cancer by promoting cell proliferation, migration, and invasion.
CELL DEATH & DISEASE
(2023)
Article
Biochemistry & Molecular Biology
Gwen R. Buel, Huy Q. Dang, John M. Asara, John Blenis, Anders P. Mutvei
Summary: This study found that prolonged deprivation of arginine and/or leucine leads to reactivation of mTORC1 activity, reaching activation levels similar to those observed in nutrient-rich conditions. Surprisingly, this reactivation is independent of amino acid regeneration, but dependent on PI3K/Akt signaling. These findings expand our understanding of the role of mTORC1 in growth-related diseases and suggest that dietary intervention by removing leucine and/or arginine may be an ineffective therapeutic approach.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Charles L. Evavold, Iva Hafner-Bratkovic, Pascal Devant, Jasmin M. D'Andrea, Elsy M. Ngwa, Elvira Borsic, John G. Doench, Martin W. LaFleur, Arlene H. Sharpe, Jay R. Thiagarajah, Jonathan C. Kagan
Summary: The Ragulator-Rag complex is found to be necessary for GSDMD pore formation and pyroptosis in macrophages, promoting GSDMD oligomerization on the plasma membrane. Defects in GSDMD oligomerization and pore formation can be rescued by mitochondrial poisons that stimulate ROS production, and ROS modulation impacts the ability of inflammasome pathways to promote pore formation downstream of GSDMD cleavage.
Article
Biotechnology & Applied Microbiology
Zhan Chen, Yong Zhang, Xiang Wu, Ji Zhang, Wei Xu, Cheng Shen, Bing Zheng
Summary: The study showed that G alpha inhibitory subunit 1 (G alpha i1) expression is significantly increased in renal cell carcinoma (RCC) tissues, and silencing Gail inhibits proliferation and invasion of RCC cells. Additionally, G alpha i1 regulates the expression of proliferation-related proteins in RCC cells.
ONCOTARGETS AND THERAPY
(2021)
Article
Biochemistry & Molecular Biology
Takuya Kano, Ryosuke Tsumagari, Akio Nakashima, Ushio Kikkawa, Shuji Ueda, Minoru Yamanoue, Nobuyuki Takei, Yasuhito Shirai
Summary: DGK beta is an enzyme that plays a crucial role in inducing neurite outgrowth by activating the mTORC1 pathway, contributing to higher brain functions such as emotion and memory. Interaction with RalA and activation of PLD and mTORC1 are key steps in DGK beta-induced neurite outgrowth.