miR-196b-5p-enriched extracellular vesicles from tubular epithelial cells mediated aldosterone-induced renal fibrosis in mice with diabetes

Hu, Renzhi; Li, Xuan; Peng, Chuan; Gao, Ruifei; Ma, Linqiang; Hu, Jinbo; Luo, Ting; Qing, Hua; Wang, Yue; Ge, Qian; Wang, Zhihong; Wu, Chaodong; Xiao, Xiaoqiu; Yang, Jun; Young, Morag J.; Li, Qifu

doi:10.1136/bmjdrc-2019-001101

Cited by 27 publications

(12 citation statements)

References 36 publications

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“…Stress hormones (GC and NE), an Akt-specific inhibitor (perifosine), or receptor antagonists were added to the culture medium for intervention. Based on successful activation/inhibition in previous publications ( 32 , 33 ), the concentrations of all drugs were selected as follows: GC (10 µmol/l), NE (10 µmol/l), perifosine (10 µmol/l; cat. no.…”

Section: Methodsmentioning

confidence: 99%

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

et al. 2021

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High malignancy and high mortality of glioma render it urgent to elucidate the underlying mechanisms of glioma carcinogenesis and explore novel targets for therapy. Epidemiologic and clinical studies have revealed that chronic stress promotes the progression of various solid tumors and is correlated with poor prognosis; however, findings reporting the involvement of chronic stress in glioma are rare. In the present study, a chronic restraint animal model and a chronic stress cell model were established to explore the effects of chronic stress on glioma and its molecular mechanisms. The results revealed that chronic stress promoted glioma growth in vivo, and the serum levels of the stress hormones glucocorticoid (GC) and noradrenaline (NE) were significantly increased. In addition, GC and NE were verified to accelerate the proliferation of glioma cells in vitro. Mechanistically, the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway was revealed to be activated under stress conditions, and inhibition of the expression of p-Akt could restrain the stress hormone-induced glioma cell proliferation. In addition, our data indicated that the GC receptor (GR) and β-adrenergic receptors (ADRBs) were both required for the biological functions of GC and NE in glioma cells. In conclusion, these results indicated that chronic stress and the stress hormones GC and NE activated PI3K/Akt signaling through binding to GR and ADRBs, thereby promoting glioma cell growth. Our findings may provide potential therapeutic targets and pave the way for the development of new strategies to protect patients with glioma from the detrimental effects of stress on tumor progression.

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Section: Methodsmentioning

confidence: 99%

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

et al. 2021

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“…Upon EVs being released from their producer TEC, transglutaminase 2 promoted fibrogenic pathways via direct binding interactions with ECM proteins and stimulation of myofibroblast functions [ 114 ]. Aldosterone-induced renal fibrosis in db/db mice involved export of EV miR-196b-5p from TEC and its delivery into fibroblasts resulting in downregulation of suppressor of cytokine signaling 2 (SOCS2) expression and enhanced expression of signal transducer and activator of transcription 3 ( STAT3 ), FN , αSMA , or collagen1α1 [ 115 ].…”

Section: Renal Fibrosismentioning

confidence: 99%

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Brigstock

2021

Cells

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Fibrosis is the unrelenting deposition of excessively large amounts of insoluble interstitial collagen due to profound matrigenic activities of wound-associated myofibroblasts during chronic injury in diverse tissues and organs. It is a highly debilitating pathology that affects millions of people globally and leads to decreased function of vital organs and increased risk of cancer and end-stage organ disease. Extracellular vesicles (EVs) produced within the chronic wound environment have emerged as important vehicles for conveying pro-fibrotic signals between many of the cell types involved in driving the fibrotic response. On the other hand, EVs from sources such as stem cells, uninjured parenchymal cells, and circulation have in vitro and in vivo anti-fibrotic activities that have provided novel and much-needed therapeutic options. Finally, EVs in body fluids of fibrotic individuals contain cargo components that may have utility as fibrosis biomarkers, which could circumvent current obstacles to fibrosis measurement in the clinic, allowing fibrosis stage, progression, or regression to be determined in a manner that is accurate, safe, minimally-invasive, and conducive to repetitive testing. This review highlights the rapid and recent progress in our understanding of EV-mediated fibrotic pathogenesis, anti-fibrotic therapy, and fibrosis staging in the lung, kidney, heart, liver, pancreas, and skin.

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“…miR-196b-5p could directly target the tumor suppressor, thus accelerating tumor cell proliferation, migration, and cell cycle (43,44). In addition, it was reported that miR-196b-5p was remarkably enriched in cells-derived exosomes, generating crosstalk between different types of cell (47,48). This study found that miR-196b-5p was a potential highly expressed miRNA in HemSCs-exos by RNA sequencing analysis.…”

Section: Discussionmentioning

confidence: 67%

Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B

Wang¹,

Zhao²,

Liu³

et al. 2021

Ann Transl Med

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Background: Though infantile hemangioma (IH) is a common benign vascular tumor, its pathogenesis remains unclear. This study explored the function of hemangioma-derived stem cells (HemSCs) derived exosomes, which exerted an intercellular effect on hemangioma-derived endothelial cells (HemECs).Methods: First, HemSCs and HemECs were extracted and cultured. HemSCs derived exosomes (HemSCsexos) were harvested. miRNA sequencing and target prediction were used to explore differentially expressed miRNAs and potential binding targets. After HemECs were co-cultured with HemSCs-exos, a series of in vitro assays were then performed including cell counting kit-8 (CCK-8) assay, cell apoptosis assay, cell cycle assay and tube formation assay to evaluate proliferation, angiogenesis abilities, etc. qRT-PCR and Western blot were conducted to detect the expression level of target genes and proteins.Results: After co-culturing with HemSCs-exos, proliferation, and angiogenesis abilities of HemECs were enhanced, while apoptosis and cell cycle arrest rate were decreased. MiR-196b-5p was observed to be significantly highly expressed in HemSCs-exos. CDKN1B was identified as the binding target of miR-196b-5p. HemECs' proliferation and angiogenesis abilities were elevated when co-cultured with exosomes from HemSCs transfected with miR-196b-5p mimic. In addition, apoptosis rate declined, and lower cells were arrested in G0/G1 phases. Cyclin E, bcl-2 were significantly highly expressed, whereas p27, Bax expression were significantly down-regulated. The positive effect of miR-196b-5p in HemSCs-exos was dramatically reversed when HemECs were transfected with oe-CDKN1B. Conclusions:The current study found a novel intercellular interaction between IH cells. Briefly, exosomederived miRNA-196b-5p in HemSCs could facilitate proliferation and angiogenesis abilities, and attenuate apoptosis and cell cycle repression rate of HemECs by directly binding with CDKN1B.

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miR-196b-5p-enriched extracellular vesicles from tubular epithelial cells mediated aldosterone-induced renal fibrosis in mice with diabetes

Cited by 27 publications

References 36 publications

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

Chronic stress promotes glioma cell proliferation via the PI3K/Akt signaling pathway

Extracellular Vesicles in Organ Fibrosis: Mechanisms, Therapies, and Diagnostics

Exosome-derived miR-196b-5p facilitates intercellular interaction in infantile hemangioma via down-regulating CDKN1B

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