https://ir.ymlib.yonsei.ac.kr/handle/22282913/168760 2026-05-30T11:02:54Z 2026-05-30T11:02:54Z Lim, Yongwoon Jeong, Anna Kwon, Duk-Hwa Lee, Yun-Gyeong Lee, Yeong-Un Cho, Hye Jung Kee, Hae Jin Yoon, Somy Yoon, Ho-Geun Kim, Yugyeong Seo, Sang Beom Nam, Kwang-Il Eom, Gwang Hyeon Ahn, Youngkeun Yong, Jeongsik Kim, Young-Kook Kook, Hyun https://ir.ymlib.yonsei.ac.kr/handle/22282913/212150 2026-05-12T08:36:02Z 2026-04-01T00:00:00Z

Title: Loss of p300/CBP-associated factor aggravates cardiac remodeling via regulation of CAMKK2 acetylation Authors: Lim, Yongwoon; Jeong, Anna; Kwon, Duk-Hwa; Lee, Yun-Gyeong; Lee, Yeong-Un; Cho, Hye Jung; Kee, Hae Jin; Yoon, Somy; Yoon, Ho-Geun; Kim, Yugyeong; Seo, Sang Beom; Nam, Kwang-Il; Eom, Gwang Hyeon; Ahn, Youngkeun; Yong, Jeongsik; Kim, Young-Kook; Kook, Hyun Abstract: Here we aim to elucidate the role of the p300/CBP-associated factor (PCAF) in pathological cardiac remodeling. Specifically, we explore how PCAF-mediated acetylation of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) influences AMPK signaling, thereby regulating cardiac hypertrophy and dysfunction under pathological stress. A genetically engineered PCAF-knockout (KO) mouse model was generated using the CRISPR-Cas9 system to evaluate the effect of PCAF deficiency on cardiac remodeling induced by isoproterenol infusion and transverse aortic constriction (TAC). PCAF deficiency significantly aggravated cardiac enlargement with features of eccentric hypertrophy, as demonstrated by histological analysis and echocardiography. To determine these phenotypes were cardiomyocyte specific, we generated a cardiomyocyte-specific conditional KO model, which also showed a dilated cardiomyopathy-like phenotype similar to that of the global-KO mice. Transcriptomic analysis of TAC-operated hearts from wild-type and KO mice revealed enrichment of pathways related to mitochondrial function and energy homeostasis. Mechanistically, PCAF directly acetylated CAMKK2, promoting its activation and the subsequent phosphorylation of AMP-activated protein kinase alpha (AMPK alpha) at Thr172, a critical step in maintaining metabolic balance under stresses. These signaling alterations were also observed in the hearts of PCAF-KO hearts subjected to isoproterenol administration or TAC. Pharmacological activation of PCAF with SPV106 effectively attenuated TAC-induced cardiac remodeling, preserving cardiac structure and function. Collectively, these findings identify PCAF as a pivotal regulator of pathological cardiac remodeling through modulation of the CAMKK2-AMPK signaling axis. Loss of PCAF exacerbates stress-induced cardiac hypertrophy and dysfunction, highlighting its potential as a therapeutic target to preserve cardiac function and counteract stress-induced remodeling.

2026-04-01T00:00:00Z Su, Yan Kwon, Soon Kyu Choi, Hack Sun Han, Yunjon Park, Jung-Hee Jang, Yong-Suk Choi, Jong Hyun Seo, Jeong-Woo https://ir.ymlib.yonsei.ac.kr/handle/22282913/212130 2026-05-12T08:35:50Z 2026-04-01T00:00:00Z

Title: EPA-Derived diHEPAs Attenuate Lipopolysaccharide-Induced Acute Lung Injury by Regulating Inflammation and Redox Homeostasis Authors: Su, Yan; Kwon, Soon Kyu; Choi, Hack Sun; Han, Yunjon; Park, Jung-Hee; Jang, Yong-Suk; Choi, Jong Hyun; Seo, Jeong-Woo Abstract: Acute lung injury (ALI) is characterized by excessive inflammation, oxidative stress, and impaired resolution responses, partly driven by dysregulated macrophage activation. In this study, a defined mixture of eicosapentaenoic acid (EPA)-derived dihydroxyeicosapentaenoic acids (diHEPAs), comprising 5,15-diHEPA and 8,15-diHEPA at an equimolar ratio, was generated using soybean lipoxygenase and its protective effects on lipopolysaccharide (LPS)-induced ALI were investigated. Mice were orally administered 5,15-diHEPA (40 mu g/kg), 8,15-diHEPA (40 mu g/kg), or the diHEPA mixture (20 mu g/kg each) for 7 days before LPS challenge. LPS exposure induced severe lung injury, as evidenced by an increased lung wet/dry ratio, inflammatory cell infiltration, and oxidative stress. Treatment with diHEPAs attenuated lung pathological damage, reduced proinflammatory cytokine production, and restored redox homeostasis. Consistently, in vitro studies in RAW264.7 macrophages showed that the diHEPA mixture suppressed LPS-induced inflammatory responses through the inhibition of NF-kappa B signaling and rebalanced oxidative stress via modulation of the NOX2/Nrf2/HO-1/ROS axis. Altogether, these results indicate that EPA-derived diHEPAs confer protection against ALI by suppressing inflammation and restoring redox balance, emphasizing their potential as therapeutic agents for ALI.

2026-04-01T00:00:00Z Kim, Woong Yim, Ye-Seal Baek, Jung-Hwan Park, Young Soo Song, Ji-Joon Chung, Joon-Yong Gim, Jungsoo Kim, Seok-Jun Chun, Kyung-Hee https://ir.ymlib.yonsei.ac.kr/handle/22282913/212393 2026-05-22T07:32:34Z 2026-04-01T00:00:00Z

Title: Nuclear Galectin-1 Drives Cancer Progression through O-GlcNAcylation-Dependent Regulation of SOX2 Authors: Kim, Woong; Yim, Ye-Seal; Baek, Jung-Hwan; Park, Young Soo; Song, Ji-Joon; Chung, Joon-Yong; Gim, Jungsoo; Kim, Seok-Jun; Chun, Kyung-Hee Abstract: Galectin-1 is frequently upregulated in tumors and contributes to cancer progression. Here, we identify galectin-1 as a critical regulator of cancer stem-like properties. Silencing galectin-1 suppressed proliferation, motility, side population fraction, and tumorsphere formation in vitro, and impaired tumor initiation and growth in vivo, whereas overexpression enhanced these malignant phenotypes. Transcriptomic profiling revealed stemness-associated transcription factors as major downstream targets, with SOX2 emerging as a key effector. Galectin-1 knockdown reduced SOX2 expression, whereas overexpression increased SOX2 nuclear abundance and transcriptional activity. Rescue experiments demonstrated that SOX2 is functionally required for galectin-1-mediated stemness and tumorigenesis. Mechanistically, galectin-1 associates with SOX2 in an O-GlcNAcylation-dependent manner. Inhibition of O-GlcNAcylation or mutation of SOX2 O-GlcNAc sites disrupted this interaction, reduced SOX2 transcriptional activity, and impaired tumorsphere formation, supporting an intracellular lectin-like function. Structural modeling predicted that residues E71 and R73 within the carbohydrate recognition domain are critical for carbohydrate-mediated recognition of O-GlcNAc-modified SOX2, which was validated by mutagenesis. Clinically, galectin-1 was highly expressed in gastric tumors, correlated with advanced stage, and predicted poor prognosis. Notably, high co-expression of galectin-1 and SOX2 was significantly associated with unfavorable survival outcomes. These findings establish galectin-1 as a reader-like protein that functionally engages O-GlcNAcylated SOX2 and highlight the galectin-1/SOX2 axis as a potential therapeutic target in gastric cancer.

2026-04-01T00:00:00Z Byun, Seunghee Kim, Hyunsik Lee, Sun-Ho Kwon, Jae-Hwan Kim, Hyunseung Yoo, Jung-Yoon Park, Soo-Yeon Yoon, Ho-Geun https://ir.ymlib.yonsei.ac.kr/handle/22282913/211500 2026-03-25T08:23:54Z 2026-02-01T00:00:00Z

Title: Deubiquitinase USP2 promotes hepatic stellate cell activation via p300 stabilization Authors: Byun, Seunghee; Kim, Hyunsik; Lee, Sun-Ho; Kwon, Jae-Hwan; Kim, Hyunseung; Yoo, Jung-Yoon; Park, Soo-Yeon; Yoon, Ho-Geun Abstract: Hepatic stellate cell (HSC) activation is a central mechanism in liver fibrosis, with histone acetyltransferase p300 acting as a pivotal transcriptional cofactor. To define upstream regulators of p300 stability during HSC activation, we performed a deubiquitinase inhibitor screen in activated HSCs and identified ubiquitin carboxyl-terminal hydrolase 2 (USP2) as a p300 deubiquitinase. Single-cell RNA sequencing of fibrotic human liver tissues revealed USP2 as the most specifically expressed USP family member in stromal populations, including HSCs, with marked upregulation in chronic liver disease and advanced metabolic dysfunction-associated steatotic liver disease (MASLD). Moreover, we demonstrated that USP2 stabilizes p300 and promotes HSC activation, whereas USP2 knockdown or pharmacological inhibition suppresses p300 accumulation and fibrogenic responses. These findings identify USP2 as a key regulator of p300 stability and HSC activation in liver fibrosis.Impact statement Our study identifies USP2 as a novel regulator of p300 stability and hepatic stellate cell activation, revealing a previously unrecognized mechanism driving liver fibrosis. These findings provide new insight into fibrogenesis and highlight USP2 as a potential therapeutic target, impacting both fundamental biology and translational fibrosis research.

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