https://scholarworks.korea.ac.kr/kumedicine/handle/2020.sw.kumedicine/648 2026-04-04T23:09:36Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/80158 Title: ATF6 expression governs megakaryocyte maturation through dual regulatory mechanisms Authors: Lee, Se-Ryeon; Lee, Yu-Seon; Kim, Jungsun; Jeong, Sang Hoon; Lee, Ju-Han; Sung, Hwa-Jung; Lee, Hong Abstract: BackgroundMegakaryocytes expand their genomes and secretory capacity to produce platelets, which burden the endoplasmic reticulum (ER) with a high proteostatic load. The role of activating transcription factor 6 (ATF6) in this setting has remained elusive.ObjectiveTo define the role of ATF6 in regulating ER proteostasis and megakaryocyte maturation in MEG-01 cells cultured without PMA, and to identify key mediators that relay ATF6-dependent transcriptional and secretory reprogramming.ResultsIncreasing ATF6 levels increased the unfolded protein response activity, ER-associated degradation, N-linked glycosylation, autophagy, AMPK and sirtuin signaling, and DNA repair linked to TP53, while reducing microRNA biogenesis, pre-mRNA processing, and senescence signatures. The knockdown exhibited a reciprocal pattern. Upstream analyses pointed to the restraint of proliferative drivers and support for genomic surveillance. Changes in ATF6 levels are relayed by SNURF and EGR1 to reshape megakaryocyte programs. SNURF and EGR1 function as positive and negative effectors, respectively. SNURF gain-of-function reinforced the unfolded protein response core, canonical megakaryocyte transcription factors, terminal maturation factors, and genes that preserved genome stability and shifted the secretome toward TIMP-1 and osteoprotegerin. EGR1 produced the opposite effects and reweighted interleukin-6, interleukin-1 beta, and interleukin-8. Class I MHC pathways changed in the same direction as the intracellular programs.ConclusionAltogether, these results define an ATF6-centered circuit that links endomitosis, proteostasis, genome integrity, and effector output, and provide a mechanistic rationale to explore whether targeted modulation can improve ex vivo platelet production and adjust thromboinflammatory signaling. 2026-03-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79483 Title: MT1B overexpression enhances malignancy of non-small cell lung cancer cells Authors: Park, Yoon Hee; LEE, Hong; Kim, Haewon; Park, Hayan; Park, Su A.; Choi, Jin Young; Park, Chaewon; Nam, Yoon Jeong; Lee, Hye Jin; Lee, Yu-Seon; Kim, Jea young; Lee, Byoungcheun; Kim, Hye-Jin; Lee, Ju Han; Jeong, Sang Hoon Abstract: Metallothioneins (MTs) are metal-binding proteins that are involved in heavy metal homeostasis and protection against oxidative stress. The MT1 family comprises several isoforms that are implicated in various diseases, including cancer. Although the dysregulated expression of MT1 isoforms has been observed in lung cancer, the specific role of MT isoform MT1B remains unclear. To investigate the role of MT1B in lung cancer progression, A549 lung cancer cells were transfected with an MT1B expression vector. In vitro assays were performed to assess cell viability, migration, invasion, and colony formation. Western blot analysis revealed increased expression of epithelial-mesenchymal transition (EMT) markers Snail, Vimentin, and N-cadherin, and decreased levels of E-cadherin, indicating EMT induction. In the xenograft model, the MT1B-transfected group formed tumors more rapidly and exhibited significantly increased tumor growth compared to the controls. In addition, RNA sequencing was performed to identify MT1B-dependent gene alterations, and Ingenuity Pathway Analysis (IPA) was applied to characterize the canonical pathways and predicted biological functions associated with these MT1B-specific genes. These findings suggest that cellular MT1B overexpression has the potential to promote lung cancer growth. [BMB Reports 2026; 59(2): 161-168] 2026-02-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/79010 Title: Developmental exposure to benzalkonium chloride induces defects in mechanosensory hair cells and nociceptive responses in zebrafish Authors: Kim, Yeonhwa; Cho, Yuji; Jeon, Eun Jung; Jeong, Sang Hoon; Park, Eun-Kee; Park, Hae-Chul; Lee, Ju-Han; Kim, Suhyun Abstract: Sensory neurotoxicity involves damage to the sensory nerves, often resulting from exposure to chemicals, medications, toxins, infections, or neurological disorders. Benzalkonium chloride (BKC) is a widely used quaternary ammonium compound with antiseptic properties, commonly present in pharmaceuticals, household products, and cosmetics. While the potential neurotoxicity of BKC has been previously explored in ocular and nasal epithelia, its impact on other sensory systems and the underlying mechanisms remain largely unclear. In this study, we used zebrafish (Danio rerio) embryos to assess the developmental neurotoxicity of BKC. Embryonic exposure to 0.72, 1.28, and 2.24 mg/L BKC led to dose-dependent impairments in mechanosensory hair cells, reduced startle responses, and heightened nociceptive sensitivity upon noxious stimulation. BKC exposure induced pronounced oxidative stress, evidenced by increased reactive oxygen species levels, reduced antioxidant enzyme activity, and altered expression of redox-regulating genes. Moreover, BKC significantly upregulated inflammatory and pain-associated genes, including tnfa, il1b, cox2, bdnf, and trpa1b. Expression profiling of hair cell differentiation markers revealed increased pou4f3 and decreased tmc2a/tmc2b, suggesting that BKC disrupts both terminal differentiation and mechanotransduction processes in sensory hair cells. Collectively, these findings uncover a novel mechanistic link between oxidative stress, impaired hair-cell maturation, and sensory dysfunction, offering new insights into the mechanisms underlying BKC-induced sensory neurotoxicity. This study emphasizes the ecological and toxicological relevance of quaternary ammonium compounds in aquatic environments. 2026-01-01T00:00:00Z https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/77092 Title: Lung neoplasm development in a mouse model exposed to fine particulate matter in Korea Authors: Oh, Hyunseung; Nam, Yoon Jeong; Choi, Jin Young; Lee, Hyejin; Lee, Hong; Lee, Yu-Seon; Park, Yoon Hee; Park, Su A.; Park, Hayan; Kim, Jaeyoung; Jeong, Sang Hoon; Lee, Ju-Han Abstract: Background: South Korea has one of the highest levels of fine particulate matter (PM2.5) exposure among Organization for Economic Co-operation and Development (OECD) member countries, while also experiencing a combination of external and domestic sources. Therefore, PM2.5 collected from South Korean air with these characteristics is an optimal sample for animal studies focused on analyzing the potential effects of PM2.5 on human health. Evidence from numerous human cohort studies and animal experiments suggests that chronic exposure to PM2.5 significantly increases the risk of lung cancer. However, most of these studies relied on commercially available PM2.5 rather than samples collected directly from ambient air. Objectives: This study aimed to investigate the pathology of how PM2.5 collected directly from the ambient air affects the development of neoplasms, fibrosis, and inflammation in the lung tissue of animal models. Tumors were categorized according to pathological classification as hyperplasia, adenoma, or carcinoma. Results: The mean number of adenomas was significantly higher in the urethane + PM group than in the saline group. The mean maximum adenoma diameters in the urethane + PM and PM groups were significantly greater than in the saline group. In addition, the mean maximum adenoma diameter in the urethane + PM group was significantly greater than in the urethane group. Conclusion: Our data show that exposure to PM influences the formation and growth of lung adenomas. Further studies are needed to elucidate the long-term effects of PM exposure and its underlying mechanisms, which could aid in developing preventive strategies. © The Author(s) under exclusive licence to The Korean Society of Toxicogenomics and Toxicoproteomics 2025. 2025-12-01T00:00:00Z