A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization

Chen, Jinying; Lin, Fan-Li; Leung, J.; Tu, Leilei; Wang, Jiang-Hui; Chuang, Yu-Fan; Fan, Li; Shen, Hsin‐Hui; Dusting, Gregory J.; Wong, Vickie; Lisowski, Leszek; Hewitt, Alex W.; Bui, Bang V.; Zhong, Jingxiang; Liu, Guei‐Sheung

doi:10.1007/s10456-020-09745-7

Cited by 23 publications

(16 citation statements)

References 24 publications

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“…When the myocardial cell membrane is damaged, LDH is rapidly released from the cells in the culture medium. Therefore, LDH can be used as an indicator of cell damage caused by H/R [ 58 , 59 ]. Our data showed that LATS2 suppression significantly reduced the LDH content in the medium and this effect was dependent on the PGC1 α -associated mitochondrial biogenesis [ 60 – 62 ].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

Chen

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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Reperfusion therapy is the most effective treatment for acute myocardial infarction, but it can damage cardiomyocytes through a mechanism known as myocardial ischemia/reperfusion injury (MIRI). In this study, we investigated whether the large tumor suppressor kinase 2 (LATS2) contributes to the development of myocardial MIRI by disrupting mitochondrial biogenesis. Our in vitro data demonstrate that cardiomyocyte viability was reduced and apoptosis was increased in response to hypoxia/reoxygenation (H/R) injury. However, suppression of LATS2 by shRNA sustained cardiomyocyte viability by maintaining mitochondrial function. Compared to H/R-treated control cardiomyocytes, cardiomyocytes transfected with LATS2 shRNA exhibited increased mitochondrial respiration, improved mitochondrial ATP generation, and more stable mitochondrial membrane potential. LATS2 suppression increased cardiomyocyte viability and mitochondrial biogenesis in a manner dependent on PGC1α, a key regulator of mitochondrial metabolism. These results identify LATS2 as a new inducer of mitochondrial damage and myocardial MIRI and suggest that approaches targeting LATS2 or mitochondrial biogenesis may be beneficial in the clinical management of cardiac MIRI.

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Section: Discussionmentioning

confidence: 99%

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

Chen

Liu

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…LPS-associated myocardial damage could be attenuated by MKP-1 through reducing inflammatory response [63]. Oxidative stress-mediated endothelial cell injury was associated with ER stress due to a loss of MKP-1 activity [64,65]. Overexpression of MKP-1 reduced ER stress, resulting in increased neural cell survival [66].…”

Section: Discussionmentioning

confidence: 99%

[Retracted] MKP‐1 Overexpression Reduces Postischemic Myocardial Damage through Attenuation of ER Stress and Mitochondrial Damage

Hou¹,

Li²,

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Mitochondrial dysfunction and endoplasmic reticulum (ER) stress contribute to postischemic myocardial damage, but the upstream regulatory mechanisms have not been identified. In this study, we analyzed the role of mitogen-activated protein kinase (MAPK) phosphatase 1 (MKP-1) in the regulation of mitochondrial function and ER stress in hypoxic cardiomyocytes. Our results show that MKP-1 overexpression sustains viability and reduces hypoxia-induced apoptosis among H9C2 cardiomyocytes. MKP-1 overexpression attenuates ER stress and expression of ER stress genes and improves mitochondrial function in hypoxia-treated H9C2 cells. MKP-1 overexpression also increases ATP production and mitochondrial respiration and attenuates mitochondrial oxidative damage in hypoxic cardiomyocytes. Moreover, our results demonstrate that ERK and JNK are the downstream signaling targets of MKP-1 and that MKP-1 overexpression activates ERK, while it inhibits JNK. Inhibition of ERK reduces the ability of MKP-1 to preserve mitochondrial function and ER homeostasis in hypoxic cardiomyocytes. These results show that MKP-1 plays an essential role in the regulation of mitochondrial function and ER stress in hypoxic H9C2 cardiomyocytes through normalization of the ERK pathway and suggest that MKP-1 may serve as a novel target for the treatment of postischemic myocardial injury.

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“…After 30 min, PI was removed, and the cells were washed twice with the medium [ 33 ]. The number of PI-positive cells was determined using fluorescence microscopy with an excitation of 535 nm and emission of 617 nm at 200x magnification [ 34 ].…”

Section: Methodsmentioning

confidence: 99%

Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis

Zhang

Han

et al. 2021

Journal of Oncology

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Although the incidence of thyroid carcinoma has increased over the past several decades, it has an excellent prognosis and overall 5-year survival, with a stable mortality rate, except in cases with advanced stages or rare malignant tumor types. Biomarkers have emerged as effective targets of molecular therapy against thyroid carcinoma due to their rapid and convenient detection; however, there has been little clinical application. Macrophage stimulating 2 (Mst2) is a proapoptotic protein with implications in carcinogenesis and metastasis. We found that Mst2 overexpression-induced endoplasmic reticulum (ER) stress in MDA-T32 thyroid carcinoma cells, accompanied by elevated caspase-12 activity, increased apoptotic rate, and reduced cell viability. In addition, Mst2 overexpression contributed to mitochondrial damage, as evidenced by increased mitochondrial oxidative stress and activated the mitochondrial apoptotic pathway. Inhibition of the JNK pathway abolished these effects. These results show Mst2 to be a novel tumor suppressor that induces mitochondrial dysfunction and ER stress via the JNK pathway. Thus, Mst2 could potentially serve as a biomarker for developing targeted therapy against thyroid carcinoma.

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A drug-tunable Flt23k gene therapy for controlled intervention in retinal neovascularization

Cited by 23 publications

References 24 publications

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

[Retracted] LATS2 Deletion Attenuates Myocardial Ischemia‐Reperfusion Injury by Promoting Mitochondrial Biogenesis

[Retracted] MKP‐1 Overexpression Reduces Postischemic Myocardial Damage through Attenuation of ER Stress and Mitochondrial Damage

Mst2 Overexpression Inhibits Thyroid Carcinoma Growth and Metastasis by Disrupting Mitochondrial Fitness and Endoplasmic Reticulum Homeostasis

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