MicroRNA-137 and its downstream target LSD1 inversely regulate anesthetics-induced neurotoxicity in dorsal root ganglion neurons

Chen, Lingyang; Wang, Xiaodan; Wen-guang, Huang; Ying, Tingting; Chen, Minjuan; Cao, Jianbin; Wang, Mingcang

doi:10.1016/j.brainresbull.2017.09.004

Cited by 18 publications

(14 citation statements)

References 22 publications

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“…Interestingly, our former research con rmed a positive role of miR-137 in LSD1 expression, which was contrary to several studies reporting that miR-137 directly binds to LSD1 [23,26,51,52]. The contradicted outcomes might be associated with the various biological features of different cell types, and we deduced that there probably exist intermediary regulators working between miR-137 and LSD1 during the osteogenesis of hASCs.…”

Section: Discussioncontrasting

confidence: 99%

A NOTCH1/LSD1/BMP2 Co-Regulatory Network Mediated by miR-137 Negatively Regulates Osteogenesis of Human Adipose-Derived Stem Cells

Fan

Wang

et al. 2020

Preprint

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Background: MicroRNAs have been recognized as critical regulators for the osteoblastic lineage differentiation of human adipose-derived stem cells (hASCs). Previously, we have displayed that silencing of miR-137 enhances the osteoblastic differentiation potential of hASCs partly through the coordination of lysine-specific histone demethylase 1 (LSD1), bone morphogenetic protein 2 (BMP2), and mothers against decapentaplegic homolog 4 (SMAD4). However, still numerous molecules involved in the osteogenic regulation of miR-137 remain unknown. This study aimed to further elucidate the epigenetic mechanisms of miR-137 on the osteogenic differentiation of hASCs.Methods: hASCs transfected with miR-137 overexpression or knockdown lentiviruses were used to assess the osteogenic capacity by testing the alkaline phosphatase activity, matrix mineralization degree, relative expression level of osteogenesis-associated genes and ectopic osteogenesis in nude mice. Dual-luciferase reporter assay was performed to examine the targeting of the 3' untranslated region (3' UTR) of NOTCH1 by miR-137. Interrelationships of signaling pathways of NOTCH1-hairy and enhancer of split 1 (HES1), LSD1, and BMP2-SMAD4 were thoroughly investigated by separate knockdown of NOTCH1, LSD1, and BMP2.Results: We confirmed that miR-137 directly targeted the 3' UTR of NOTCH1 while positively regulated HES1. After knocking down NOTCH1 or BMP2 individually, we found that these two signals formed a positive feedback loop and activated LSD1. In addition, LSD1 knockdown induced the expression of NOTCH1 while suppressed HES1.Conclusions: Collectively, we proposed a NOTCH1/LSD1/BMP2 co-regulatory signaling network to elucidate the modulation of miR-137 on the osteoblastic differentiation of hASCs, thus providing mechanism-based rationale for miRNA-targeted therapy of bone defect.

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Section: Discussioncontrasting

confidence: 99%

A NOTCH1/LSD1/BMP2 Co-Regulatory Network Mediated by miR-137 Negatively Regulates Osteogenesis of Human Adipose-Derived Stem Cells

Fan

Wang

et al. 2020

Preprint

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“…Our previous studies confirmed that the genetic knockdown or chemical blockade of LSD1 could promote the osteogenic differentiation of MSCs (Ge et al, ; Lv et al, ). LSD1 is reported to serve as a target gene of miR‐137 in neural stem cells, neuroblastoma cells, dorsal root ganglion neurons, non‐small‐cell lung cancer cells, and endometrial cancer cells (Althoff et al, ; Chen et al, ; J. Q. Sun et al, ; W. Zhang et al, ; X. Zhang, Zhang, Yu, Hu, & Hao, ), but whether it could also be directly targeted by miR‐137 in hASCs still needs to be identified.…”

Section: Introductionmentioning

confidence: 99%

MiR‐137 knockdown promotes the osteogenic differentiation of human adipose‐derived stem cells via the LSD1/BMP2/SMAD4 signaling network

Fan

Wang

et al. 2019

Journal Cellular Physiology

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MicroRNAs are a group of endogenous regulators that participate in several cellular physiological processes. However, the role of miR-137 in the osteogenic differentiation of human adipose-derived stem cells (hASCs) has not been reported. This study verified a general downward trend in miR-137 expression during the osteogenic differentiation of hASCs. MiR-137 knockdown promoted the osteogenesis of hASCs in vitro and in vivo. Mechanistically, inhibition of miR-137 activated the bone morphogenetic protein 2 (BMP2)-mothers against the decapentaplegic homolog 4 (SMAD4) pathway, whereas repressed lysine-specific histone demethylase 1 (LSD1), which was confirmed as a negative regulator of osteogenesis in our previous studies. Furthermore, LSD1 knockdown enhanced the expression of BMP2 and SMAD4, suggesting the coordination of LSD1 in the osteogenic regulation of miR-137. This study indicated that miR-137 negatively regulated the osteogenic differentiation of hASCs via the LSD1/BMP2/SMAD4 signaling network, revealing a new potential therapeutic target of hASC-based bone tissue engineering.

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“…1,2 However, clinical studies indicated that exposure to LAs for long duration or at high dosage may cause spinal neurotoxicity or may induce nonreversible neurological complications. [3][4][5] Moreover, LAs also may cause postsurgical nervous complications. 1 For example, bupivacaine (BUP) acts as a LA and is extensively used for epidural anesthesia, nerve blockade and postoperative analgesia in clinical patients.…”

Section: Introductionmentioning

confidence: 99%

<p>Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage</p>

Wang¹,

Xia²,

Qiao³

et al. 2019

DDDT

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Background: Bupivacaine (BUP) acts as a local anesthetic, which is extensively used for clinical patients but could generate neurotoxicity in neurons. Tetramethylpyrazine (TET) exhibits strong neuron protective effects against neurotoxicity. Hence, we investigate the effect of TET on BUP-induced neurotoxicity in SH-SY5Y cells. Methods: CCK-8 assay was used to detect cell proliferation in SH-SY5Y cells. In addition, Western blotting was used to examine Bax, Bcl-2, active caspase 3, LC3II, Beclin 1 and p-62 protein levels in cells. Moreover, ELISA assay was used to detect the levels of total glutathione (GS), superoxide dismutase (SOD) and malondialdehyde (MDA) in cells. Results: In this study, we found that TET attenuated the neurotoxicity of BUP on SH-SY5Y cells. Meanwhile, TET alleviated BUP-induced apoptosis in SH-SY5Y cell via decreasing the expressions of active caspase-3 and Bax and increasing the expression of Bcl-2. In addition, monodansylcadaverine staining assay and Western blotting results confirmed that TET induced autophagy in SH-SY5Y cells via increasing the LC3II/I and Beclin 1 levels. Furthermore, TET attenuated BUP-induced oxidative damage in SH-SY5Y cells via upregulation of the levels of total GS and SOD and downregulation of the level of MDA. Interesting, the protective effects of TET against BUP-induced neurotoxicity in SH-SY5Y cells were reversed by autophagy inhibitor 3-methyladenine (3MA). Conclusion: These data indicated that TET may play a neuroprotective role via inhibiting apoptosis and inducing autophagy in SH-SY5Y cells. Therefore, TET may be a potential agent for the treatment of human neurotoxicity induced by BUP.

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MicroRNA-137 and its downstream target LSD1 inversely regulate anesthetics-induced neurotoxicity in dorsal root ganglion neurons

Cited by 18 publications

References 22 publications

A NOTCH1/LSD1/BMP2 Co-Regulatory Network Mediated by miR-137 Negatively Regulates Osteogenesis of Human Adipose-Derived Stem Cells

A NOTCH1/LSD1/BMP2 Co-Regulatory Network Mediated by miR-137 Negatively Regulates Osteogenesis of Human Adipose-Derived Stem Cells

MiR‐137 knockdown promotes the osteogenic differentiation of human adipose‐derived stem cells via the LSD1/BMP2/SMAD4 signaling network

<p>Tetramethylpyrazine attenuated bupivacaine-induced neurotoxicity in SH-SY5Y cells through regulating apoptosis, autophagy and oxidative damage</p>

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