MiR-373 exacerbates renal injury and fibrosis via NF-κB/MatrixMetalloproteinase-9 signaling by targeting Sirtuin1

Yang, Huihui; Liao, Dongmei; Tong, Liang; Zhong, Ling; Wu, Keng‐Liang

doi:10.1016/j.ygeno.2018.04.017

Cited by 12 publications

(7 citation statements)

References 37 publications

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“…Table 2 (Ref. [3,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]) displays the primer sequences applied in this research.…”

Section: Rna Isolation and Quantitative Real-time Pcrmentioning

confidence: 99%

Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice

Wang¹,

Liu²,

Chang³

et al. 2022

Front. Biosci. (Landmark Ed)

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Background: Non-alcoholic fatty liver disease (NAFLD) has become a prevalent issue and a consequence of metabolic syndrome impact on human health. Both of anti-atherosclerosis and anti-hepatic fibrosis capabilities of herbal medicine Ger-Gen-Chyn-Lian-Tang (GGCLT) has attracted attention, but their molecular regulatory mechanisms in a NAFLD model have not been elucidated. The aim of the present study was to explore the bioactivity of db/db mice following treatment with GGCLT. Methods: NAFLD phenotype of db/db mice were treated with GGCLT and lipogenesis, mitochondria dysfunction, mitophagy, macrophage polarization and adipose tissue browning were then evaluated using qRT-PCR and/or Western blot analysis, immunofluorescence, and immunohistochemistry assays, respectively. Results: GGCLT not only decreased serum levels of TG and free fatty acids, but glucose and insulin tolerance test in db/db mice. In parallel, GGCLT reduced lipogenesis and hypoxia-inflammation cascades in NAFLD progression. GGCLT reduced lipid accumulation and was accompanied by the enhanced mitochondria biogenesis, M2 macrophage, and decreased M1 macrophage. The latter two events contributing to the anti-inflammation are resulting from mitochondria dynamics, and the lipotoxicity lowering effect of GGCLT of NAFLD mice is mediated by promoting mitophagy in Parkin-dependent and -independent pathways, by mitochondrial fusion over fission manner. GGCLT also inactivated lipogenesis and decreased lipid accumulation in epididymal white adipose tissue with a higher M2/M1 macrophage ratio. Conclusions: Besides in the liver, modulating of mitochondrial biogenesis and adipose tissue browning were characterized by increased Tmem26, Tfam, and Prdm16 expression by GGCLT in EWAT also contributes to the beneficial action in NAFLD.

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“…Table 2 (Ref. [3,[23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38]) displays the primer sequences applied in this research.…”

Section: Rna Isolation and Quantitative Real-time Pcrmentioning

confidence: 99%

Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice

Wang¹,

Liu²,

Chang³

et al. 2022

Front. Biosci. (Landmark Ed)

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“…It is well recognized that cell apoptosis is controlled by two major pathways: namely the extrinsic death receptor-mediate pathway and intrinsic then activated caspase-9, caspase-3, and PARP (14,15). The former is activated at the plasma membrane via binding to extracellular ligand, such as FasL and TRAIL, leading to the cleavage of caspase-8 (26,27).…”

Section: Discussionmentioning

confidence: 99%

“…The former is activated at the plasma membrane via binding to extracellular ligand, such as FasL and TRAIL, leading to the cleavage of caspase-8 (26,27). On the other hand, the activation of intrinsic pathway results in cytochrome c release from mitochondria to cytosol, which in turn cleaves caspase-9, caspase-3, and PARP (14). Thus, each apoptotic pathway activates corresponding initiator caspase, caspase-8, or caspase-9.…”

Section: Discussionmentioning

confidence: 99%

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ClC-5 Downregulation Induces Osteosarcoma Cell Apoptosis by Promoting Bax and tBid Complex Formation

Peng

Cai

et al. 2021

Front. Oncol.

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Osteosarcoma is the most common malignant bone tumor. Chloride (Cl−) channels-mediated Cl− movement plays an important role in regulating the functions of various cancer cells, but its role in osteosarcoma remains unclear. In this study, we found that ClC-5 was increased in osteosarcoma tissues compared with normal bone tissues. Patients with high ClC-5 expression showed poor overall survival relative to those patients with low ClC-5 expression. Higher ClC-5 expression and lower intracellular Cl− concentration ([Cl−]i) were observed in osteosarcoma cells compared with normal osteoblasts. Lowering [Cl−]i increased the viability of osteosarcoma cells, which was markedly blocked by ClC-5 downregulation. Knockdown of ClC-5 significantly induced osteosarcoma cell apoptosis and increased the release of cytochrome c from mitochondria to cytosol, concomitantly with cleavage of caspase-9, caspase-3, and PARP. The effect of ClC-5 downregulation on osteosarcoma cell apoptosis and viability was abolished by caspase-3 and caspase-9 inhibitors, but not caspase-8 inhibitor. Furthermore, ClC-5 inhibition promoted Bax translocation from cytosol to mitochondria. Immunoprecipitation showed that ClC-5 interacted with Bax and ClC-5 downregulation enhanced Bax and tBid complex formation. Collectively, we demonstrate that ClC-5 downregulation induces osteosarcoma cell apoptosis via mitochondria-dependent apoptotic pathway activation by promoting Bax and tBid association and subsequent Bax translocation.

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“…For example, miR-128 has been reported to targes PPARγ to promote the progression of Alzheimer's disease (14). In addition, miR-373 has been reported to aggravate renal fibrosis by targeting Sirtuin 1 and regulating NF-κB/MMP-9 signaling (15). miR-129-5p inhibition may contribute to IDD development by accelerating NP cell apoptosis by targeting BMP2 (16).…”

Section: Introductionmentioning

confidence: 99%

miR‑654‑5p inhibits autophagy by targeting ATG7 via mTOR signaling in intervertebral disc degeneration

et al. 2021

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Intervertebral disc degeneration (IDD) is a common chronic disease characterized by the loss of extracellular matrix (ECM) in the nucleus pulposus (NP). Accumulating evidence has revealed that abnormal expression of microRNAs (miRs) is closely associated with IDD development. The present study aimed to investigate the precise role and possible mechanism underlying the effects of miR-654-5p in the pathogenesis of IDD. NP cells were isolated from patients with IDD. Monodansylcadaverine staining was conducted to reveal cell autophagy, while western blotting was performed to detect the expression of ECM-related proteins in NP cells. Luciferase reporter and RNA immunoprecipitation assays were conducted to identify the binding between RNAs. The results demonstrated that miR-654-5p was significantly upregulated in degenerated NP tissues from patients with IDD and high miR-654-5p expression was positively associated with disc degeneration grade. Functional assays suggested that miR-654-5p facilitated ECM degradation by increasing the expression levels of MMP-3, MMP-9 and MMP-13, as well as decreasing collagen I, collagen II, SOX9 and aggrecan expression by inhibiting autophagy. Furthermore, autophagy-related gene 7 (ATG7) was verified as a direct downstream target gene of miR-654-5p. miR-654-5p could bind to the 3' untranslated region of ATG7 to inhibit its mRNA expression and further reduce its translation. Notably, ATG7 knockdown abrogated the effects of the miR-654-5p inhibitor on ECM degradation and autophagy regulation. Furthermore, miR-654-5p inhibited autophagy in NP cells by increasing the protein expression levels of phosphorylated (p)-PI3K, p-AKT and p-mTOR in an ATG7-dependent manner. In conclusion, the results of the present study revealed that miR-654-5p may enhance ECM degradation via inhibition of autophagy by targeting ATG7 to activate the PI3K/AKT/mTOR signaling pathway. These findings may provide novel insights into the treatment of IDD.

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MiR-373 exacerbates renal injury and fibrosis via NF-κB/MatrixMetalloproteinase-9 signaling by targeting Sirtuin1

Abstract: These results indicated an undesired effect of miR-373 in the regulation of renal injury and fibrosis by targeting SIRT1-mediated NF-κB/MMP-9 signaling, which might provide a potential therapeutic strategy for renal fibrosis.

Cited by 12 publications

References 37 publications

Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice

Antioxidants Rich Herbal Formula Ger-Gen-Chyn-Lian-Tang Protects Lipotoxicity and Ameliorates Inflammation Signaling through Regulation of Mitochondrial Biogenesis and Mitophagy in Nonalcoholic Fatty Liver Disease Mice

ClC-5 Downregulation Induces Osteosarcoma Cell Apoptosis by Promoting Bax and tBid Complex Formation

miR‑654‑5p inhibits autophagy by targeting ATG7 via mTOR signaling in intervertebral disc degeneration

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