Simvastatin alleviates airway inflammation and remodelling through up‐regulation of autophagy in mouse models of asthma

Gu, Wen; Cui, Rong; Ding, Tao; Li, Xiaoming; Peng, Juan; Xu, Weiguo; Han, Fengfeng; Guo, Xuejun

doi:10.1111/resp.12926

Cited by 63 publications

(47 citation statements)

References 33 publications

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“…For example, hepatocytes of mice fed with statin for 16 weeks showed prominent vacuolization and autophagosomes, as assessed by TEM analysis [66]. Intraperitoneal daily injection of 20 mg/kg simvastatin for 12 weeks induces an increase in autophagy-related proteins Atg5, LC3b and Beclin1 expression and autophagosome formation [67]. …”

Section: Induction Of Autophagy In Mouse Modelsmentioning

confidence: 99%

Methods for Measuring Autophagy in Mice

Moulis

Vindis

2017

Cells

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Autophagy is a dynamic intracellular process that mediates the degradation of damaged cytoplasmic components by the lysosome. This process plays important roles in maintaining normal cellular homeostasis and energy balance. Measuring autophagy activity is critical and although the determination of autophagic flux in isolated cells is well documented, there is a need to have reliable and quantitative assays to evaluate autophagy in whole organisms. Because mouse models have been precious in establishing the functional significance of autophagy under physiological or pathological conditions, we present in this chapter a compendium of the current available methods to measure autophagy in mice, and discuss their advantages and limitations.

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Section: Induction Of Autophagy In Mouse Modelsmentioning

confidence: 99%

Methods for Measuring Autophagy in Mice

Moulis

Vindis

2017

Cells

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“…Autophagy plays an essential role in pulmonary inflammation during asthma progress (Gu et al, ; J. N. Liu et al, ). Airway inflammation involves the induction of autophagy (Yin et al, ).…”

Section: Introductionmentioning

confidence: 99%

Chrysophanol attenuates airway inflammation and remodeling through nuclear factor‐kappa B signaling pathway in asthma

Song

Zhang

et al. 2019

Phytotherapy Research

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Chrysophanol (CHR), a purified active constituent extracted from Rheum palmatum L., possesses anti-inflammatory activity. This study aimed to evaluate its effects on asthma-associated airway inflammation and remodeling. BALB/c mice were sensitized and challenged by ovalbumin (OVA) and administrated with different doses of CHR. We found that CHR decreased OVA-induced pulmonary inflammation: the levels of interleukin (IL)-4, IL-5, and IL-13, tumor necrosis factor (TNF)-α, and inducible nitric oxide synthase were downregulated. CHR also attenuated airway remodeling induced by OVA challenge-CHR inhibited pulmonary α-smooth muscle actin expression. Moreover, both the nuclear translocation and activity of NF-κB p65 were inhibited by CHR in the asthmatic lung. Enhanced autophagy was initiated in the lung by OVA challenge as evidenced by upregulated light chain 3 beta, autophagyrelated protein 5, and Beclin 1. CHR suppressed OVA-induced alterations in these autophagy-related molecules. In vitro, CHR (2 or 20 μM) was used to treat human pulmonary epithelial BEAS-2B cells in the presence of 10 ng/ml recombinant TNF-α. CHR not only exhibited the antiproliferation effect but also inhibited the activation of nuclear factor-kappa B (NF-kB) signaling pathway in TNF-α-treated BEAS-2B cells. In conclusion, our study indicates that CHR has the potential to ameliorate asthma.

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“…However, the effects of simvastatin on osteogenic differentiation of jaw‐derived BMSCs and osteoclast activity involved in dental implant osseointegration remain to be further investigated. Interestingly, recent studies have shown that simvastatin mediates the function of nerve (Gao et al, ), muscle (Whitehead, ; Whitehead, Kim, Bible, Adams, & Froehner, ), and smooth muscle cells (Gu et al, ) via up‐regulation of autophagy and alleviation of ROS. Notably, activation of autophagy and suppression of ROS levels contributed to increased osteogenic differentiation of BMSCs.…”

Section: Introductionmentioning

confidence: 99%

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

Shi

et al. 2018

J Tissue Eng Regen Med

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Dental implants have become a widely accepted and successful treatment for fully and partially edentulous patients. Simvastatin has been applied to improve and accelerate the osseointegration of implants by increasing the quantity and quality of bone tissue. However, its potential mechanism has not been elucidated completely. Here, we found that simvastatin significantly enhanced the autophagy level of jaw-derived bone marrow stromal cells (BMSCs) and alleviated production of reactive oxygen species under unfavourable conditions. Simvastatin promoted osteogenic differentiation of BMSCs via enhanced autophagy. Furthermore, simvastatin inhibited the bone resorption activity of osteoclasts. With the use of a rat model of oral implant osseointegration, we found local injection of simvastatin displayed more new bone formation at the interface of the bone and implant compared with that of oral administration. Fluorochrome labelling histomorphometrical analysis and micro-CT also showed that simvastatin promoted the osseointegration of implants. Notably, fewer activated osteoclasts were observed in the region of osseointegration of implants from the simvastatin treatment groups, especially the local delivery of simvastatin. Collectively, our results revealed that simvastatin can increase osteoblastic differentiation of BMSCs via enhanced autophagy and decreased osteoclast activity. Thus, simvastatin could be a viable and promising drug to improve and even accelerate the osseointegration of a dental implant.

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Simvastatin alleviates airway inflammation and remodelling through up‐regulation of autophagy in mouse models of asthma

Abstract: These findings demonstrate that simvastatin inhibits airway inflammation and airway remodelling through an activated autophagic process in BSMCs. We propose a crucial function of autophagy in statin-based therapeutic approaches in asthma.

Cited by 63 publications

References 33 publications

Methods for Measuring Autophagy in Mice

Methods for Measuring Autophagy in Mice

Chrysophanol attenuates airway inflammation and remodeling through nuclear factor‐kappa B signaling pathway in asthma

Simvastatin improves oral implant osseointegration via enhanced autophagy and osteogenesis of BMSCs and inhibited osteoclast activity

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