Long noncoding RNA NEAT1 accelerates the proliferation and fibrosis in diabetic nephropathy through activating Akt/mTOR signaling pathway

Diabetic nephropathy (DN) is the most common complication of diabetes and is prone to kidney failure. Dihydromyricetin (DHM) has been reported to have a variety of pharmacological activities. This study aims to explore the effect of DHM on DN and the underlying molecular mechanism. An in vivo DN rat model was established. The degree of renal interstitial fibrosis (RIF) was detected by hematoxylin-eosin (HE) staining, Masson's trichrome staining, and immunohistochemistry (IHC). In vitro, NRK-52E cells were divided into four groups: normal glucose (NG), high glucose (HG), HG+DHM, and HG+rapamycin (autophagy inhibitor). The levels of autophagy- and fibrosis-related proteins were analyzed by western blotting. The expression of miR-155-5p and phosphatase and tensin homolog deleted on chromosome ten (PTEN) and their relationship were assessed by quantitative reverse transcription (qRT)-PCR and dual luciferase reporter gene assay. Our results showed that RIF was increased in DN rat model and in HG-induced NRK-52E cells. DHM treatment attenuated the increased RIF and also increased autophagy. MiR-155-5p expression was increased, while PTEN expression was decreased in DN rat and cell model, and DHM reversed both effects. Dual luciferase assay showed that PTEN was the target gene of miR-155-5p. DHM inhibited HG-induced fibrosis and promoted autophagy by inhibiting miR-155-5p expression in NRK-52E cells. In addition, DHM promoted autophagy by inhibiting the PI3K/AKT/mTOR signaling pathway. In conclusion, DHM promotes autophagy and attenuates RIF by regulating the miR-155-5p/PTEN signaling and PI3K/AKT/mTOR signaling pathway in DN.

Download Full-text

Emerging Role of mTOR Signaling-Related miRNAs in Cardiovascular Diseases

Oxidative Medicine and Cellular Longevity ◽

10.1155/2018/6141902 ◽

2018 ◽

Vol 2018 ◽

pp. 1-23 ◽

Cited By ~ 7

Author(s):

Arun Samidurai ◽

Rakesh C. Kukreja ◽

Anindita Das

Keyword(s):

Cardiovascular Diseases ◽

Cardiovascular System ◽

Signaling Pathway ◽

Noncoding Rna ◽

Current Knowledge ◽

Mammalian Target Of Rapamycin ◽

Vital Role ◽

Mtor Signaling ◽

Cellular Growth ◽

Mtor Signaling Pathway

Mechanistic/mammalian target of rapamycin (mTOR), an atypical serine/threonine kinase of the phosphoinositide 3-kinase- (PI3K-) related kinase family, elicits a vital role in diverse cellular processes, including cellular growth, proliferation, survival, protein synthesis, autophagy, and metabolism. In the cardiovascular system, the mTOR signaling pathway integrates both intracellular and extracellular signals and serves as a central regulator of both physiological and pathological processes. MicroRNAs (miRs), a class of short noncoding RNA, are an emerging intricate posttranscriptional modulator of critical gene expression for the development and maintenance of homeostasis across a wide array of tissues, including the cardiovascular system. Over the last decade, numerous studies have revealed an interplay between miRNAs and the mTOR signaling circuit in the different cardiovascular pathophysiology, like myocardial infarction, hypertrophy, fibrosis, heart failure, arrhythmia, inflammation, and atherosclerosis. In this review, we provide a comprehensive state of the current knowledge regarding the mechanisms of interactions between the mTOR signaling pathway and miRs. We have also highlighted the latest advances on mTOR-targeted therapy in clinical trials and the new perspective therapeutic strategies with mTOR-targeting miRs in cardiovascular diseases.

Download Full-text

Thioredoxin interacting protein (TXNIP) regulates tubular autophagy and mitophagy in diabetic nephropathy through the mTOR signaling pathway

Scientific Reports ◽

10.1038/srep29196 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 37

Author(s):

Chunling Huang ◽

Yuan Zhang ◽

Darren J. Kelly ◽

Christina Y. R. Tan ◽

Anthony Gill ◽

...

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Interacting Protein ◽

Thioredoxin Interacting Protein

Download Full-text

miRNA‑214 suppresses oxidative stress in diabetic nephropathy via the ROS/Akt/mTOR signaling pathway and uncoupling protein 2

Experimental and Therapeutic Medicine ◽

10.3892/etm.2019.7359 ◽

2019 ◽

Cited By ~ 10

Author(s):

Shufang Yang ◽

Xiaoqiang Fei ◽

Yu Lu ◽

Bangkui Xu ◽

Yongmei Ma ◽

...

Keyword(s):

Oxidative Stress ◽

Diabetic Nephropathy ◽

Signaling Pathway ◽

Uncoupling Protein ◽

Mtor Signaling ◽

Uncoupling Protein 2 ◽

Mtor Signaling Pathway

Download Full-text

LncRNA Hoxb3os protects podocytes from high glucose-induced cell injury through autophagy dependent on the Akt-mTOR signaling pathway

Acta Biochimica Polonica ◽

10.18388/abp.2020_5483 ◽

2021 ◽

Author(s):

Juan Jin ◽

Jianguang Gong ◽

Li Zhao ◽

Yiwen Li ◽

Qiang He

Keyword(s):

Diabetic Nephropathy ◽

Signaling Pathway ◽

High Glucose ◽

Cell Injury ◽

Damage Model ◽

Mtor Signaling ◽

Cell Counting ◽

Tunel Staining ◽

Mtor Signaling Pathway ◽

Potential Biomarker

Background: Diabetic nephropathy (DN) is in the first place of the causes that lead to end-stage renal disease in the world. Thus, it is urgent to develop a novel diagnostic or therapeutic strategy that could stop the progression of diabetic nephropathy. Methods: RNA-sequencing was conducted in high glucose (HG)-treated MPC5 cells (podocytes). Cell morphology was examined under a light microscope. Upon high-glucose challenge, the effects of lncRNA Hoxb3os overexpression on MPC5 cells apoptosis, viability, autophagy and Akt-mTOR signaling were evaluated using flow cytometry, Cell Counting Kit-8, qRT-PCR, and Western blotting. TUNEL staining and ELISA were performed to confirm the establishment of DN model in db/db mice. Results: High-glucose exposure dramatically altered lncRNA expression profile in MPC5 cells (fold change>2), including 305 upregulated lncRNAs and 451 downregulated lncRNAs. LncRNA Hoxb3os expression was significantly reduced in the HG-induced podocyte damage model, as well as in the renal tissues from db/db mice with spontaneous DN. Overexpression of Hoxb3os significantly reduced the apoptosis rate and increased the viability of MPC5 cells under HG conditions. Further study revealed that exogenous Hoxb3os increased autophagy level in HG-exposed MPC5 cells via abrogating Akt-mTOR signaling pathway and that the process was possibly implicated in the upregulation of SIRT1. Conclusion: LncRNA Hoxb3os protected podocytes from HG-induced damage by regulating Akt-mTOR pathway and cell autophagy. Thus, lncRNA Hoxb3os appears as a potential biomarker in the diagnosis and treatment of DN in the future.

Download Full-text