Review : Multi-phenotypic Role of Serum Response Factor in the Gastrointestinal System

( Seungil Ro ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2016 Journal of Neurogastroenterology and Motility (JNM Vol.22 No.2

Serum response factor (SRF) is a master transcription factor of the actin cytoskeleton that binds to highly conserved CArG boxes located within the majority of smooth muscle cell (SMC)-restricted promoters/enhancers. Although most studies of SRF focus on skeletal muscle, cardiac muscle, and vascular SMCs, SRF research has recently expanded into the gastrointestinal (GI) system. Genome scale analyses of GI SMC transcriptome and CArG boxes (CArGome) have identified new SRF target genes. In addition to circular and longitudinal smooth muscle layers, SRF is also expressed in GI mucosa and cancers. In the GI tract, SRF is the central regulator of genes involved in apoptosis, dedifferentiation, proliferation, and migration of cells. Since SRF is the cell phenotypic modulator, it may play an essential role in the development of myopathy, hypertrophy, ulcers, gastric and colon cancers within the GI tract. Given the multifunctional role displayed by SRF in the digestive system, SRF has received more attention emerging as a potential therapeutic target. This review summarizes the findings in SRF research pertaining to the GI tract and provides valuable insight into future directions. (J Neurogastroenterol Motil 2016;22:193-200)

Upregulation of autophagy by Ginsenoside Rg2 in MCF-7 cells

정유헌,정슬아,최현석,Seungil Ro,이정섭,박종군 한국통합생물학회 2018 Animal cells and systems Vol.22 No.6

Autophagy is a major intracellular degradation process that plays an important role in cell survival, stress responses, nutrient sensing and development. Our previous studies have shown that Rg2, a triterpenoid saponin contained in ginseng, protects cells against UVB-induced genotoxicity by increasing DNA repair, in possible association with modulation of protein levels involved in p53 pathway. In this study, we determined an upregulation of autophagy by Rg2. Rg2 treatment for 24 h in MCF-7, a breast cancer cell, did not show cytotoxicity up to 200 μM. Rg2 also upregulated the level of p-p53, p-AMPK, p-ACC, Atg-7 and LC3-II and decreased the level of p62 in concentration-dependent manners. We also determined the level of p53, AMPK, p62, Atg-7 and LC3 after UVB exposure and subsequent incubation in growth medium for 24 h. UVB increased the level of p-p53, p-AMPK, p-ACC and decreased the levels of p62, Atg-7 and LC3-II. Interestingly, Rg2 treatment for 24 h after UVB exposure increased the levels of p-p53, p-AMPK, p-ACC, Atg-7 and LC3-II and decreased the level of cyclobutane pyrimidine dimer, a UVB-induced DNA damage in concentration-dependent manners. All these results suggest that Rg2 increased autophagy and decreased UVB-induced DNA damage, in possible association with the modulation of protein levels in p53- and autophagic pathways.

Role of DNA Methylation in the Development and Differentiation of Intestinal Epithelial Cells and Smooth Muscle Cells

Brian G Jorgensen,Seungil Ro 대한소화기 기능성질환∙운동학회 2019 Journal of Neurogastroenterology and Motility (JNM Vol.25 No.3

The mammalian intestine contains many different cell types but is comprised of 2 main cell types: epithelial cells and smooth musclecells. Recent in vivo and in vitro evidence has revealed that various alterations to the DNA methylation apparatus within both of thesecell types can result in a variety of cellular phenotypes including modified differentiation status, apoptosis, and uncontrolled growth. Methyl groups added to cytosines in regulatory genomic regions typically act to repress associated gene transcription. AberrantDNA methylation patterns are often found in cells with abnormal growth/differentiation patterns, including those cells involved inburdensome intestinal pathologies including inflammatory bowel diseases and intestinal pseudo-obstructions. The altered methylationpatterns being observed in various cell cultures and DNA methyltransferase knockout models indicate an influential connectionbetween DNA methylation and gastrointestinal cells’ development and their response to environmental signaling. As these modifiedDNA methylation levels are found in a number of pathological gastrointestinal conditions, further investigations into uncovering thecausative nature, and controlled regulation, of this epigenetic modification is of great interest.

Protective effects of ginsenoside Rg2 and astaxanthin mixture against UVB-induced DNA damage

정유헌,정슬아,최현석,Seungil Ro,이정섭,박종군 한국통합생물학회 2018 Animal cells and systems Vol.22 No.6

Ultraviolet B (UVB) radiation induces skin damage, skin matrix degradation, and wrinkle formation through photochemical reaction and oxidative stress. Therefore, protecting the skin from UVB can prevent skin aging. In this study, we investigated the effects of a mixture (RA) of Rg2, a ginsenoside, and astaxanthin, an antioxidant, on the responses of HaCaT cells exposed to UVB (700 J/m2). The cells were incubated for 24 h after UVB exposure and cell viability was determined by MTT assay. UVB decreased cell viability by 60% compared to that of untreated control cells, whereas RA increased cell viability in a concentration-dependent manner, and this increase was significantly higher than that in the single treatment groups. Further, UVB increased the levels of DNA lesions such as cyclobutane pyrimidine dimer (CPD) and 8-hydroxyguanine (8-OHdG). Conversely, RA decreased both CPD and 8-OHdG levels in a concentration-dependent manner. UVB exposure also increased phosphorylation of ataxia-telangiectasia mutated (ATM) protein kinase and p53 and subsequently increased the levels of GADD45α, p21, and matrix metalloproteinases (MMPs)- 3, -9, and -13. Additionally, UVB exposure decreased the level of COL1A1. However, RA treatment decreased the levels of p-ATM, p-p53, GADD45α, p21, MMP-3, -9, and -13 and increased the level of COL1A1 in a concentration-dependent manner. These results suggest that RA reduces UVBinduced cytotoxicity and genotoxicity through up-regulation of DNA repair via the combined effects of Rg2 and astaxanthin.

Upregulation of autophagy by Ginsenoside Rg2 in MCF-7 cells

Chung, Yuheon,Jeong, Seula,Choi, Hyun Seok,Ro, Seungil,Lee, Jung Sup,Park, Jong Kun ZOOLOGICAL SOCIETY OF KOREA 2018 ANIMAL CELLS AND SYSTEMS Vol.22 No.6

<P><B>ABSTRACT</B></P><P>Autophagy is a major intracellular degradation process that plays an important role in cell survival, stress responses, nutrient sensing and development. Our previous studies have shown that Rg2, a triterpenoid saponin contained in ginseng, protects cells against UVB-induced genotoxicity by increasing DNA repair, in possible association with modulation of protein levels involved in p53 pathway. In this study, we determined an upregulation of autophagy by Rg2. Rg2 treatment for 24 h in MCF-7, a breast cancer cell, did not show cytotoxicity up to 200 μM. Rg2 also upregulated the level of p-p53, p-AMPK, p-ACC, Atg-7 and LC3-II and decreased the level of p62 in concentration-dependent manners. We also determined the level of p53, AMPK, p62, Atg-7 and LC3 after UVB exposure and subsequent incubation in growth medium for 24 h. UVB increased the level of p-p53, p-AMPK, p-ACC and decreased the levels of p62, Atg-7 and LC3-II. Interestingly, Rg2 treatment for 24 h after UVB exposure increased the levels of p-p53, p-AMPK, p-ACC, Atg-7 and LC3-II and decreased the level of cyclobutane pyrimidine dimer, a UVB-induced DNA damage in concentration-dependent manners. All these results suggest that Rg2 increased autophagy and decreased UVB-induced DNA damage, in possible association with the modulation of protein levels in p53- and autophagic pathways.</P>

Protective effects of ginsenoside Rg2 and astaxanthin mixture against UVB-induced DNA damage

Chung, Yu Heon,Jeong, Seul A.,Choi, Hyun Seok,Ro, Seungil,Lee, Jung Sup,Park, Jong Kun ZOOLOGICAL SOCIETY OF KOREA 2018 ANIMAL CELLS AND SYSTEMS Vol.22 No.6

<P><B>ABSTRACT</B></P><P>Ultraviolet B (UVB) radiation induces skin damage, skin matrix degradation, and wrinkle formation through photochemical reaction and oxidative stress. Therefore, protecting the skin from UVB can prevent skin aging. In this study, we investigated the effects of a mixture (RA) of Rg2, a ginsenoside, and astaxanthin, an antioxidant, on the responses of HaCaT cells exposed to UVB (700 J/m<SUP>2</SUP>). The cells were incubated for 24 h after UVB exposure and cell viability was determined by MTT assay. UVB decreased cell viability by 60% compared to that of untreated control cells, whereas RA increased cell viability in a concentration-dependent manner, and this increase was significantly higher than that in the single treatment groups. Further, UVB increased the levels of DNA lesions such as cyclobutane pyrimidine dimer (CPD) and 8-hydroxyguanine (8-OHdG). Conversely, RA decreased both CPD and 8-OHdG levels in a concentration-dependent manner. UVB exposure also increased phosphorylation of ataxia-telangiectasia mutated (ATM) protein kinase and p53 and subsequently increased the levels of GADD45α, p21, and matrix metalloproteinases (MMPs)-3, -9, and -13. Additionally, UVB exposure decreased the level of COL1A1. However, RA treatment decreased the levels of p-ATM, p-p53, GADD45α, p21, MMP-3, -9, and -13 and increased the level of COL1A1 in a concentration-dependent manner. These results suggest that RA reduces UVB-induced cytotoxicity and genotoxicity through up-regulation of DNA repair via the combined effects of Rg2 and astaxanthin.</P>

Gut Microbial Dysbiosis in the Pathogenesis of Gastrointestinal Dysmotility and Metabolic Disorders

( Rajan Singh ),( Hannah Zogg ),( Lai Wei ),( Allison Bartlett ),( Uday C Ghoshal ),( Singh Rajender ),( Seungil Ro ) 대한소화기기능성질환·운동학회(구 대한소화관운동학회) 2021 Journal of Neurogastroenterology and Motility (JNM Vol.27 No.1

Of all microorganisms in the human body, the largest and most complex population resides in the gastrointestinal (GI) tract. The gut microbiota continuously adapts to the host environment and serves multiple critical functions for their hosts, including regulating host immunity, procuring energy from food, and preventing the colonization of pathogens. Mounting evidence has suggested gut microbial imbalance (dysbiosis) as a core pathophysiology in the development of GI motility and metabolic disorders, such as irritable bowel syndrome and diabetes. Current research has focused on discovering associations between these disorders and gut microbial dysbiosis; however, whether these associations are a consequence or cause is still mostly unexplored. State-of-the-art studies have investigated how gut microbes communicate with our body systems through microbiota-derived metabolites and how they are able to modulate host physiology. There is now mounting evidence that alterations in the composition of small intestinal microbes have an association with GI dysmotility and metabolic disorders. Although treatment options for gut microbial dysbiosis are currently limited, antibiotics, fecal microbiota transplantation, probiotics, and dietary interventions are currently the best options. However, treatment with broad-spectrum antibiotics has been viewed with skepticism due to the risk of developing antibiotic resistant bacteria. Studies are warranted to elucidate the cellular and molecular pathways underlying gut microbiota-host crosstalk and for the development of a powerful platform for future therapeutic approaches. Here, we review recent literature on gut microbial alterations and/or interactions involved in the pathophysiology of GI dysmotility and metabolic disorders. (J Neurogastroenterol Motil 2021;27:19-34)