Role of glutathione and other antioxidants in the inhibition of apoptosis and mesenchymal transition in rabbit lens epithelial cells

Wang, H.J.; Zhu, Jingjing; Zheng, Guangying

doi:10.4238/2014.september.1.1

Cited by 9 publications

(6 citation statements)

References 17 publications

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“…Moreover, repeated airway epithelial cell damage and repair is a key cause of airway remodelling, because of enhancing activation of the epithelial mesenchymal trophic unit and leading to subepithelial airway fibrosis . Notably, some recent studies indicate that as a potent pleiotropic cytokine, TGF‐β1 even simultaneously induces the apoptosis and EMT in certain epithelial cells, such as renal tubular epithelial cells, mammary epithelial cells and lens epithelial cells . In this study, we have provided substantial evidence for the first time to support the concomitant airway epithelial apoptosis and EMT in OVA‐challenged mice, as indicated by apoptosis index and the induction of four well known EMT markers: E‐cadherin, N‐cadherin, α‐SMA and Snail.…”

Section: Discussionsupporting

confidence: 58%

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Liu

Zhou

et al. 2020

J Cellular Molecular Medi

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Airway epithelial apoptosis and epithelial mesenchymal transition (EMT) are two crucial components of asthma pathogenesis, concomitantly mediated by TGF‐β1. RACK1 is the downstream target gene of TGF‐β1 shown to enhancement in asthma mice in our previous study. Balb/c mice were sensitized twice and challenged with OVA every day for 7 days. Transformed human bronchial epithelial cells, BEAS‐2B cells were cultured and exposed to recombinant soluble human TGF‐β1 to induced apoptosis (30 ng/mL, 72 hours) and EMT (10 ng/mL, 48 hours) in vitro, respectively. siRNA and pharmacological inhibitors were used to evaluate the regulation of RACK1 protein in apoptosis and EMT. Western blotting analysis and immunostaining were used to detect the protein expressions in vivo and in vitro. Our data showed that RACK1 protein levels were significantly increased in OVA‐challenged mice, as well as TGF‐β1‐induced apoptosis and EMT of BEAS‐2B cells. Knockdown of RACK1 (siRACK1) significantly inhibited apoptosis and decreased TGF‐β1 up‐regulated EMT related protein levels (N‐cadherin and Snail) in vitro via suppression of JNK and Smad3 activation. Moreover, siSmad3 or siJNK impaired TGF‐β1‐induced N‐cadherin and Snail up‐regulation in vitro. Importantly, JNK gene silencing (siERK) also impaired the regulatory effect of TGF‐β1 on Smad3 activation. Our present data demonstrate that RACK1 is a concomitant regulator of TGF‐β1 induces airway apoptosis and EMT via JNK/Smad/Snail signalling axis. Our findings may provide a new insight into understanding the regulation mechanism of RACK1 in asthma pathogenesis.

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Section: Discussionsupporting

confidence: 58%

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Liu

Zhou

et al. 2020

J Cellular Molecular Medi

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“…Obvious mitophagy can be observed 12 h after TGEV infection, and can be suppressed by GSH treatment. Many reports have shown that GSH or other antioxidants treatment could effectively inhibit apoptosis caused by oxidative stress [ 60 – 62 ]. The impaired mitochondria could release ROS and other pro-apoptotic substances, such as cytochrome c, etc., to promote apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Mitophagy in TGEV infection counteracts oxidative stress and apoptosis

et al. 2016

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The intestinal epithelial cells contain a large number of mitochondria for persisting absorption and barrier function. Selective autophagy of mitochondria (mitophagy) plays an important role in the quality control of mitochondria and maintenance of cell homeostasis. Transmissible gastroenteritis virus (TGEV) is a porcine enteropathogenic coronavirus which induces malabsorption and lethal watery diarrhea in suckling piglets. The role of mitophagy in the pathological changes caused by TGEV infection is unclear. Here, we report that TGEV induces mitophagy to suppress oxidative stress and apoptosis induced by viral infection in porcine epithelial cells (IPEC-J2). We observe that TGEV infection induce mitochondrial injury, abnormal morphology, complete mitophagy, and without obvious apoptosis after TGEV infection. Meanwhile, TGEV also induces DJ-1 and some antioxidant genes upregulation to suppress oxidative stress induced by viral infection. Furthermore, silencing DJ-1 inhibit mitophagy and increase apoptosis after TGEV infection. In addition, we demonstrate for the first time that viral nucleocapsid protein (N) is located in mitochondria and mitophagosome during virus infection or be expressed alone. Those results provide a novel perspective for further improvement of prevention and treatment in TGEV infection. These results suggest that TGEV infection induce mitophagy to promote cell survival and possibly viral infection.

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“…For example, tighter control of downstream mediators and regulators of TGFß/Smad-signaling, including connective tissue growth factor (CTGF) and gremlin (Ma et al, 2014) may have a role in controlling lens pathology. Similarly, interfering with other downstream molecules involved in TGFß-mediated EMT, such as matrix metalloproteinases (Korol et al, 2014), the production of reactive oxygen species (Chamberlain et al, 2009; Wang et al, 2014) and even specific integrins (α v ; Mamuya et al, 2014) may also contribute to prevention strategies. Other gene regulators, such as miRNA-204-5p and miRNA-26b, which are reduced in PCO and cataract, and have been shown to repress TGFß-induced EMT in human lens epithelial cells (Dong et al, 2014; Wang et al, 2013), may also serve as effective modulators of pathological events.…”

Section: Sprouty: Negative Regulator Of Rtk Signaling Pathwaysmentioning

confidence: 99%

Fibrosis in the lens. Sprouty regulation of TGFβ-signaling prevents lens EMT leading to cataract

Lovicu

Shin

McAvoy

2016

Experimental Eye Research

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Cataract is a common age-related condition that is caused by progressive clouding of the normally clear lens. Cataract can be effectively treated by surgery; however, like any surgery, there can be complications and the development of a secondary cataract, known as posterior capsule opacification (PCO), is the most common. PCO is caused by aberrant growth of lens epithelial cells that are left behind in the capsular bag after surgical removal of the fiber mass. An epithelial-to-mesenchymal transition (EMT) is central to fibrotic PCO and forms of fibrotic cataract, including anterior/posterior polar cataracts. Transforming growth factor β (TGFβ) has been shown to induce lens EMT and consequently research has focused on identifying ways of blocking its action. Intriguingly, recent studies in animal models have shown that EMT and cataract developed when a class of negative-feedback regulators, Sprouty (Spry)1 and Spry2, were conditionally deleted from the lens. Members of the Spry family act as general antagonists of the receptor tyrosine kinase (RTK)-mediated MAPK signaling pathway that is involved in many physiological and developmental processes. As the ERK/MAPK signaling pathway is a well established target of Spry proteins, and overexpression of Spry can block aberrant TGFβ-Smad signaling responsible for EMT and anterior subcapsular cataract, this indicates a role for the ERK/MAPK pathway in TGFß-induced EMT. Given this and other supporting evidence, a case is made for focusing on RTK antagonists, such as Spry, for cataract prevention. In addition, and looking to the future, this review also looks at possibilities for supplanting EMT with normal fiber differentiation and thereby promoting lens regenerative processes after cataract surgery. Whilst, it is now known that the epithelial to fiber differentiation process is driven by FGF, little is known about factors that coordinate the precise assembly of fibers into a functional lens. However, recent research provides key insights into an FGF-activated mechanism intrinsic to the lens that involves interactions between the Wnt-Frizzled and Jagged/Notch signaling pathways. This reciprocal epithelial-fiber cell interaction appears to be critical for the assembly and maintenance of the highly ordered three-dimensional architecture that is central to lens function. This information is fundamental to defining the specific conditions and stimuli needed to recapitulate developmental programs and promote regeneration of lens structure and function after cataract surgery.

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Role of glutathione and other antioxidants in the inhibition of apoptosis and mesenchymal transition in rabbit lens epithelial cells

Cited by 9 publications

References 17 publications

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Dual role of RACK1 in airway epithelial mesenchymal transition and apoptosis

Mitophagy in TGEV infection counteracts oxidative stress and apoptosis

Fibrosis in the lens. Sprouty regulation of TGFβ-signaling prevents lens EMT leading to cataract

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