Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide‐induced apoptosis in mesenchymal stem cells

Choi, Yong Jun; Lee, Chang Min; Lee, Jeong Hyun; Park, See‐Hyoung; Nam, Myeong Jin

doi:10.1002/tox.22824

Cited by 11 publications

(7 citation statements)

References 33 publications

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“…It is reported that apoptosis by transfected Crispr-HGF was induced in mesenchymal stem cells [13]. Our results indicated that transfection of Crispr-HGF induces apoptosis in a time-dependent manner in Huh7 and Hep3B cells.…”

Section: Discussionsupporting

confidence: 62%

“…The CRISPR/Cas9 system was discovered as an acquired immune system, and it was observed in bacteria and archaea [13]. In CRISPR/Cas9 system, invading external DNA is processed by Cas9 nuclease into small DNA fragments, which are then incorporated into CRISPR locus of host genomes as the spacers [14].…”

Section: Introductionmentioning

confidence: 99%

“…Thus, the mechanism of CRISPR/Cas9 system has been studied in detail and it currently being used as a gene editing tool. This system allows the target gene expression to be regulated by 20 nucleotide sequences [13].…”

Section: Introductionmentioning

confidence: 99%

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Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells

Lee

Lim

Park

et al. 2021

JPM

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Background: CRISPR/Cas9 system is a prokaryotic adaptive immune response system that uses noncoding RNAs to guide the Cas9 nuclease to induce site-specific DNA cleavage. Hepatocyte growth factor (HGF) is a well-known growth factor that plays a crucial role in cell growth and organ development. According to recent studies, it has been reported that HGF promoted growth of hepatocellular carcinoma (HCC) cells. Here, we investigated the apoptotic effects in HCC cells. Methods: Crispr-HGF plasmid was constructed using GeneArt CRISPR Nuclease Vector. pMex-HGF plasmid that targets HGF overexpressing gene were designed with pMex-neo plasmid. We performed real time-polymerase chain reaction to measure the expression of HGF mRNA. We performed cell counting assay and colony formation assay to evaluate cell proliferation. We also carried out migration assay and invasion assay to reveal the inhibitory effects of Crispr-HGF in HCC cells. Furthermore, we performed cell cycle analysis to detect transfection of Crispr-HGF induced cell cycle arrest. Collectively, we performed annexin V/PI staining assay and Western blot assay. Results: In Crispr-HGF-transfected group, the mRNA expression levels of HGF were markedly downregulated compared to pMex-HGF-transfected group. Moreover, Crispr-HGF inhibited cell viability in HCC cells. We detected that wound area and invaded cells were suppressed in Crispr-HGF-transfected cells. The results showed that transfection of Crispr-HGF induced cell cycle arrest and apoptosis in HCC cells. Expression of the phosphorylation of mitogen activated protein kinases and c-Met protein was regulated in Crispr-HGF-transfected group. Interestingly, we found that the expression of HGF protein in conditioned media significantly decreased in Crispr-HGF-transfected group. Conclusions: Taken together, we found that inhibition of HGF through transfection of Crispr-HGF suppressed cell proliferation and induced apoptotic effects in HCC Huh7 and Hep3B cells.

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Section: Discussionsupporting

confidence: 62%

Section: Introductionmentioning

confidence: 99%

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Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells

Lee

Lim

Park

et al. 2021

JPM

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“…It is proven that oxidative and nitrosative stress, caused by excessive levels of reactive oxygen species (ROS) and reactive nitrogen species (RNS), are among the crucial culprits for the inefficacy and the high mortality rates of stem cells after transplantation (Valle-Prieto & Conget, 2010). Several molecules, pathways, and mechanisms are supposed to be actively involved in the reactive speciesrelated cell death; for example, ROS-induced autophagy (Liu et al, 2015), nitric oxide (NO)-induced inactivation of nuclear factor κB (NF-κB) signaling pathway (Nakaizumi et al, 2012), and ROSinduced activation of mitogen-activated protein kinase (MAPK or MAP kinase) subfamilies which are involved in a verity of cellular and subcellular processes, including transcription, cell proliferation, cell differentiation, apoptosis, and also autophagy (Choi, Lee, Lee, Park, & Nam, 2019).…”

Section: Introductionmentioning

confidence: 99%

Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy

Panahi

Rahimi

et al. 2020

Journal Cellular Physiology

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Mesenchymal stem cells (MSCs) are earmarked as perfect candidates for cell therapy and tissue engineering due to their capacity to differentiate into different cell types. However, their potential for application in regenerative medicine declines when the levels of the reactive oxygen and nitrogen species (RONS) increase from the physiological levels, a phenomenon which is at least inevitable in ex vivo cultures and air-exposed damaged tissues. Increased levels of RONS can alter the

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“…VEGF-B protects retinal cells against oxidative stress and rescues retinal degeneration by upregulating the antioxidative genes GPX1 and SOD1 (Arjunan et al, 2018). Hepatocyte growth factor protects mesenchymal stem cells against H 2 O 2 -induced apoptosis by decreasing the phosphorylation of extracellular signal-regulated kinases and p38 (Choi et al, 2019). In this study, the therapeutic effects of ACF on photoaging are likely due to an attenuation of oxidative stress levels, an improvement in fibroblast viability, stimulation of collagen synthesis, inhibition of apoptosis, and stimulation of blood vessel formation.…”

Section: Figure 12 |mentioning

confidence: 99%

An Adipose-Derived Injectable Sustained-Release Collagen Scaffold of Adipokines Prepared Through a Fast Mechanical Processing Technique for Preventing Skin Photoaging in Mice

Jin

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Ultraviolet A (UVA) radiation is the major contributor to skin photoaging, associated with increased collagen degradation and reactive oxygen species (ROS) expression. Adipokines have been proven as promising therapeutic agents for skin photoaging. However, adipokine therapy is generally limited by the short in vivo release duration and biological instability. Therefore, developing a treatment that provides a sustained release of adipokines and enhanced therapeutic effects is desirable. In this study, we developed a novel mechanical processing technique to extract adipose tissue-derived ECM components, named the “adipose collagen fragment” (ACF). The physical characterization, injectability, collagen components, residual DNA/RNA and adipokine release pattern of ACF were identified in vitro. L929 cells were treated with ACF or phosphate-buffered saline for 24 h after UVA irradiation in vitro. The expression of senescence-associated xβ-galactosidase (SA-β-gal), ROS and antioxidase were investigated. Then, we evaluated its therapeutic efficacy by injecting ACF and phosphate-buffered saline, as a control, into the dermis of photoaging nude mice and harvesting skin samples at weeks 1, 2, and 4 after treatment for assessment. The content of adipokines released from ACF was identified in vivo. The collagen synthesis and collagen degradation in ACF implants were evaluated by immune staining. Dermal thickness, fibroblast expression, collagen synthesis, ROS level, antioxidase expression, capillary density, and apoptotic cell number were evaluated by histological assessment, immune staining, and polymerase chain reaction in the skin samples. We demonstrated that ACF is the concentrated adipose extracellular matrix collagen fragment without viable cells and can be injected through fine needles. The lower expression of SA-β-gal, ROS and higher expression of antioxidase were observed in the ACF-treated group. ACF undergoes collagen degradation and promotes neocollagen synthesis in ACF implants. Meanwhile, ACF serves as a sustained-release system of adipokines and exhibits a significantly higher therapeutic effect on mouse skin photoaging by enhancing angiogenesis, antioxidant abilities, antiapoptotic activities, and collagen synthesis through sustainedly releasing adipokines. To sum up, ACF is an adipokines-enriched, sustained-release extracellular matrix collagen scaffold that can prevent UVA-induced skin photoaging in mice. ACF may serve as a novel autologous skin filler for skin rejuvenation applications in the clinic.

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Protective effects of hepatocyte growth factor gene overexpression against hydrogen peroxide‐induced apoptosis in mesenchymal stem cells

Cited by 11 publications

References 33 publications

Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells

Knockout of Hepatocyte Growth Factor by CRISPR/Cas9 System Induces Apoptosis in Hepatocellular Carcinoma Cells

Cytoprotective effects of antioxidant supplementation on mesenchymal stem cell therapy

An Adipose-Derived Injectable Sustained-Release Collagen Scaffold of Adipokines Prepared Through a Fast Mechanical Processing Technique for Preventing Skin Photoaging in Mice

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