Review
Immunology
Xu Liu, Feng Lu, Xihang Chen
Summary: This review discusses the role of necroptotic DAMPs in tissue fibrosis and highlights the inflammatory responses induced by DAMPs in tissue ECM remodeling. By summarizing the existing literature, it provides a framework for future investigations into the relationship among necroptosis, DAMPs, and fibrosis, as well as a reference for later transformation into clinical treatment.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Endocrinology & Metabolism
Feng He, Yuanjun Ma, Shi Li, Haozhe Ren, Qian Liu, Xiaohua Chen, Hui Miao, Tao Ye, Qian Lu, Zuge Yang, Tianle Li, Xin Tong, Hongxu Yang, Mian Zhang, Helin Wang, Yazhou Wang, Shibin Yu
Summary: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease, and the role of necroptosis and downstream key DAMPs in TMJOA has been explored in this study. The research findings suggest that necroptosis contributes to cartilage degeneration and synovitis in TMJOA, and targeting the necroptotic vicious cycle may provide a potential therapeutic strategy.
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Article
Orthopedics
Lei Ding, Cheng Zhou, Hongjun Zheng, Quanming Wang, Haiyan Song, Joseph A. Buckwalter, James A. Martin
Summary: The study aimed to investigate the response of migrating chondrogenic progenitor cells (CPCs) from mechanically injured articular cartilage to proinflammatory damage-associated-molecular-patterns (DAMPs). The results showed that CPCs were more sensitive than non-CPCs in response to DAMPs, especially MTDs, indicating their critical role in early posttraumatic osteoarthritis development.
Review
Immunology
Emily Horner, Janet M. Lord, Jon Hazeldine
Summary: Major traumatic injury leads to systemic immunosuppression, and DAMPs are detected in the circulation following injury and are known to initiate the inflammatory response. Recent research suggests that DAMPs may also play a role in immune suppression after trauma.
FRONTIERS IN IMMUNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Maria Jose Caballero-Herrero, Esther Jumilla, Manuel Buitrago-Ruiz, Graciela Valero-Navarro, Santiago Cuevas
Summary: Anastomotic leakage (AL) is a severe complication in colorectal surgery, and the immune system response and DAMPs have been identified as important factors in its development. Recent research suggests that systemic concentration of DAMPs may determine the inflammatory process and contribute to the occurrence of AL and other post-surgery complications. This review provides valuable evidence for the role of DAMPs in postoperative processes and highlights the potential for new strategies to prevent post-surgical complications.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Yeongkag Kwon, Chaeyeon Park, Jueun Lee, Dong Hyun Park, Sungho Jeong, Cheol-Heui Yun, Ok-Jin Park, Seung Hyun Han
Summary: Gut microbiota plays an important role in regulating bone homeostasis by interacting with host pattern recognition receptors. Pathogenic bacteria can induce bone destruction and inflammatory bone diseases, while probiotic bacteria can prevent bone loss. Bacterial metabolites and secretory molecules also play a role in affecting bone homeostasis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Tae-Yeon Kim, Ju-Hui Kang, Se-Bin Lee, Tae-Bong Kang, Kwang-Ho Lee
Summary: This study reveals that the expression levels of key molecules involved in necroptosis are down-regulated during muscle differentiation, leading to a decreased sensitivity of differentiated muscle cells to necroptotic cell death.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Review
Chemistry, Multidisciplinary
Miao-miao Lin, Na Liu, Zheng-hong Qin, Yan Wang
Summary: Both mitochondrial dysfunction and neuroinflammation play significant roles in neurodegeneration and neurodegenerative diseases. There are multiple links between mitochondrial dysfunction and neuroinflammation, and their interaction is a complex and dynamic process. Understanding the specific molecular mechanisms associated with mitochondrial dysfunction and the progression of neuroinflammation in neurodegenerative diseases is of great importance for the identification of new therapeutic targets.
ACTA PHARMACOLOGICA SINICA
(2022)
Review
Biochemistry & Molecular Biology
Georgia K. Atkin-Smith
Summary: The clearance of dying cells is a well-defined process involving molecular factors and different mechanisms for different types of cell death. It is essential for preventing excessive release of pro-inflammatory mediators and inflammatory diseases.
BIOCHEMICAL SOCIETY TRANSACTIONS
(2021)
Review
Medicine, Research & Experimental
Po-Chun Hsieh, Yao-Kuang Wu, Mei-Chen Yang, Wen-Lin Su, Chan-Yen Kuo, Chou Chin-Lan
Summary: Acute lung injury (ALI) is a highly fatal disease characterized by diffuse pulmonary infiltrates. Damage-associated molecular patterns (DAMPs) play a crucial role in the initiation and progression of ALI. Proinflammatory cytokine overproduction, cell death, destruction of alveoli-endothelial barriers, and neutrophil infiltration are the main features of ALI. Alveolar macrophages (AMs), neutrophils, and epithelial cells (AECs) are important players in the pathogenesis of ALI.
Review
Cell Biology
Claudia M. Deus, Henrique Tavares, Margarida Beatriz, Sandra Mota, Carla Lopes
Summary: Neuroinflammation is a common feature in different neurodegenerative diseases and is associated with inflammation, oxidative stress, and mitochondrial dysfunction. Recently, a new mechanism of intercellular signaling mediated by small extracellular vesicles has been discovered. In neurodegenerative diseases, mitochondrial DAMPs play a role in initiating and exacerbating inflammation. Mitochondrial-derived vesicles are enriched in mtDAMPs and can induce an immune response and the release of pro-inflammatory cytokines.
Article
Biochemical Research Methods
Lauren P. Westhaver, Sarah Nersesian, Adam Nelson, Leah K. Maclean, Emily B. Carter, Jeanette E. Boudreau
Summary: This study describes a method for preparing mitochondrial damage-associated molecular patterns (mitoDAMPs) from mouse liver, which can be adapted for other species and tissues. The protocol yields large quantities of mitoDAMPs, facilitating research on their impacts in health and disease.
Review
Biochemistry & Molecular Biology
Na Kang, Zhenglin Ji, Yuxin Li, Ji Gao, Xinfeng Wu, Xiaoyang Zhang, Qinghui Duan, Can Zhu, Yue Xu, Luyao Wen, Xiaofei Shi, Wanli Liu
Summary: Damage-associated molecular patterns (DAMPs) derived from necrosis cells can activate DAMPs-sensing receptors and trigger inflammation. Failure to clear DAMPs can contribute to immunological diseases' pathogenesis. This review focuses on metabolite-derived DAMPs and their molecular mechanisms in exacerbating inflammation responses, as well as clinical interventions to mitigate their effects. It aims to inspire future thoughts and efforts in targeted medicinal interventions and therapy development for immunological diseases.
Article
Immunology
Zheng Liu, Rui Wan, Hua Bai, Jie Wang
Summary: In this study, a subtyping model based on damage-associated molecular pattern (DAMP) was developed to predict the prognosis and response to immunotherapy in malignant pleural mesothelioma (MPM). Through RNA sequencing analysis of 397 patients, MPMs were classified into two subtypes: the inflammatory DAMPs subtype with better prognosis and the nuclear DAMPs subtype with worse outcome. This research is important for the development of precision immunotherapy and exploration of novel immunomodulators for MPM.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Lorna S. Thorne, Garret Rochford, Timothy D. Williams, Andrew D. Southam, Giovanny Rodriguez-Blanco, Warwick B. Dunn, Nikolas J. Hodges
Summary: Cytoglobin plays a crucial role in the progression of oral squamous cell carcinoma by mediating changes in gene expression related to stress response and metabolism, protecting cells from cisplatin-induced apoptosis and oxidative stress. Lipidomic analysis revealed up-regulation of cardiolipin in cells expressing cytoglobin, suggesting a potential mechanism for cancer cells to exploit phenotypic changes and facilitate disease progression.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Yuko Kojima, Takashi Nishina, Hiroyasu Nakano, Ko Okumura, Kazuyoshi Takeda
MOLECULAR CANCER THERAPEUTICS
(2020)
Article
Multidisciplinary Sciences
Satoru Torii, Hirofumi Yamaguchi, Akira Nakanishi, Satoko Arakawa, Shinya Honda, Kenta Moriwaki, Hiroyasu Nakano, Shigeomi Shimizu
NATURE COMMUNICATIONS
(2020)
Article
Biology
Osamu Nakabayashi, Hirotaka Takahashi, Kenta Moriwaki, Sachiko Komazawa-Sakon, Fumiaki Ohtake, Shin Murai, Yuichi Tsuchiya, Yuki Koyahara, Yasushi Saeki, Yukiko Yoshida, Soh Yamazaki, Fuminori Tokunaga, Tatsuya Sawasaki, Hiroyasu Nakano
Summary: The E3 ligase MIB2 ubiquitylates apoptosis-inhibitor cFLIP, suppressing RIPK1 kinase activity-dependent and -independent apoptosis. Deletion of MIB2 enhances RIPK1 kinase activity and impairs ubiquitylation of cFLIP(L), resulting in increased apoptosis.
COMMUNICATIONS BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Takashi Nishina, Yutaka Deguchi, Daisuke Ohshima, Wakami Takeda, Masato Ohtsuka, Shigeyuki Shichino, Satoshi Ueha, Soh Yamazaki, Mika Kawauchi, Eri Nakamura, Chiharu Nishiyama, Yuko Kojima, Satomi Adachi-Akahane, Mizuho Hasegawa, Mizuho Nakayama, Masanobu Oshima, Hideo Yagita, Kazutoshi Shibuya, Tetuo Mikami, Naohiro Inohara, Kouji Matsushima, Norihiro Tada, Hiroyasu Nakano
Summary: IL-11, a member of the IL-6 family of cytokines, plays a role in tumor development. IL-11(+) cells are present in murine tumor and acute colitis models and induce the activation of colonic fibroblasts and epithelial cells. IL-11(+) fibroblasts contribute to a feed-forward loop between tumor cells and fibroblasts in the tumor microenvironment, affecting the development of colitis and colon cancer.
NATURE COMMUNICATIONS
(2021)
Article
Immunology
Kenta Moriwaki, Christa Park, Kazuha Koyama, Sakthi Balaji, Kohei Kita, Ryoko Yagi, Sachiko Komazawa-Sakon, Manami Semba, Tatsuya Asuka, Hiroyasu Nakano, Yoshihiro Kamada, Eiji Miyoshi, Francis K. M. Chan
Summary: RIPK1 plays a critical role in cell survival and death by inhibiting apoptosis and necroptosis, with loss-of-function mutations found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation can restore immune deficiency and intestinal inflammatory pathology in these patients, showing the importance of RIPK1 in maintaining intestinal immune homeostasis. Generation of DC-specific Ripk1 (-/-) mice revealed that RIPK1 is essential for colonic immune homeostasis through a scaffold activity-dependent mechanism.
MUCOSAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Manami Semba, Shinji Takamatsu, Sachiko Komazawa-Sakon, Eiji Miyoshi, Chiharu Nishiyama, Hiroyasu Nakano, Kenta Moriwaki
Summary: The study identified proscillaridin A as a promising agent that enhances the anti-cancer efficacy of TRAIL therapeutics, particularly in colon cancer cells.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Tomoya Fukuoka, Kenta Moriwaki, Shinji Takamatsu, Jumpei Kondo, Miki Tanaka-Okamoto, Azusa Tomioka, Manami Semba, Sachiko Komazawa-Sakon, Yoshihiro Kamada, Hiroyuki Kaji, Yasuhide Miyamoto, Masahiro Inoue, Kazuhiko Bessho, Yoko Miyoshi, Keiichi Ozono, Hiroyasu Nakano, Eiji Miyoshi
Summary: The study reveals that Lewis glycans positively regulate TRAIL-induced cell death, providing important insights into TRAIL sensitivity. Moreover, the expression of type I Lewis glycans is positively correlated with TRAIL sensitivity in colon cancer cell lines and patient-derived cancer organoids.
Article
Immunology
Soh Yamazaki, Naohiro Inohara, Masaki Ohmuraya, Yousuke Tsuneoka, Hideo Yagita, Takaharu Katagiri, Takashi Nishina, Tetuo Mikami, Hiromasa Funato, Kimi Araki, Hiroyasu Nakano
Summary: Deficiency of I kappa B zeta in intestinal epithelial cells leads to dysbiosis and increased abundance of segmented filamentous bacteria, exacerbating inflammatory diseases. This deficiency decreases the number of Paneth cells and impairs IL-17-inducible gene expression involved in IgA production. The study reveals the crucial role of the IL-17R-I kappa B zeta axis in the regulatory loop between gut microbiota and immune cells.
MUCOSAL IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tomohiko Murakami, Yoshifumi Takahata, Kenji Hata, Kosuke Ebina, Katsutoshi Hirose, Lerdluck Ruengsinpinya, Yuri Nakaminami, Yuki Etani, Sachi Kobayashi, Takashi Maruyama, Hiroyasu Nakano, Takehito Kaneko, Satoru Toyosawa, Hiroshi Asahara, Riko Nishimura
Summary: Proinflammatory cytokine Sema4D plays a critical role in the pathogenesis of joint diseases by directly promoting cartilage destruction. Sema4D induces a proinflammatory response in articular chondrocytes by activating proteolytic enzymes that degrade cartilage. This induction is independent of RhoA but relies on NF-kappa B signaling and Ras-MEK-Erk1/2 signaling mediated by Plexin-B2 and c-Met receptors.
Article
Multidisciplinary Sciences
Yuka Inaba, Emi Hashiuchi, Hitoshi Watanabe, Kumi Kimura, Yu Oshima, Kohsuke Tsuchiya, Shin Murai, Chiaki Takahashi, Michihiro Matsumoto, Shigetaka Kitajima, Yasuhiko Yamamoto, Masao Honda, Shun-ichiro Asahara, Kim Ravnskjaer, Shin-ichi Horike, Shuichi Kaneko, Masato Kasuga, Hiroyasu Nakano, Kenichi Harada, Hiroshi Inoue
Summary: Aggravation of liver steatosis shifts the mode of hepatocellular death from apoptosis to necroptosis, and the transcription factor ATF3 regulates this shift through the induction of RIPK3. ATF3 acts as a master regulator in this shift by inducing RIPK3 expression. The frequency of hepatocytes expressing ATF3 or RIPK3 is correlated with hepatocellular damage in non-alcoholic steatohepatitis (NASH).
NATURE COMMUNICATIONS
(2023)
Article
Multidisciplinary Sciences
Takashi Nishina, Yutaka Deguchi, Mika Kawauchi, Xiyu Chen, Soh Yamazaki, Tetuo Mikami, Hiroyasu Nakano
Summary: Intestinal homeostasis is regulated by various cells, and dysregulation of this process is related to inflammatory bowel diseases. IL-11, a member of the IL-6 family, is produced by inflammatory fibroblasts during acute colitis. In this study, it was found that IL-11 plays a protective role in DSS-induced acute colitis in mice. Deletion of Il11ra1 or Il11 increased susceptibility to colitis and led to an increase in apoptotic epithelial cells. Additionally, IL-11 production was regulated by ROS produced by myeloid cells. These findings highlight the importance of IL-11 in protecting the mucosal epithelium during acute colitis and the contribution of myeloid cell-derived ROS in attenuating colitis through IL-11 production.
Article
Biology
Shin Murai, Kanako Takakura, Kenta Sumiyama, Kenta Moriwaki, Kenta Terai, Sachiko Komazawa-Sakon, Takao Seki, Yoshifumi Yamaguchi, Tetuo Mikami, Kimi Araki, Masaki Ohmuraya, Michiyuki Matsuda, Hiroyasu Nakano
Summary: Researchers successfully generated SMART Tg mice that express the SMART biosensor in various tissues. Their findings suggest that necroptosis leads to an increase in FRET ratio in primary cells. Moreover, cisplatin-treated mice show elevated FRET signals. These results indicate that SMART Tg mice could serve as a valuable tool for monitoring necroptosis in different types of cells.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Yuichi Tsuchiya, Takao Seki, Kenta Kobayashi, Sachiko Komazawa-Sakon, Shigeyuki Shichino, Takashi Nishina, Kyoko Fukuhara, Kenichi Ikejima, Hidenari Nagai, Yoshinori Igarashi, Satoshi Ueha, Akira Oikawa, Shinya Tsurusaki, Soh Yamazaki, Chiharu Nishiyama, Tetuo Mikami, Hideo Yagita, Ko Okumura, Taketomo Kido, Atsushi Miyajima, Kouji Matsushima, Mai Imasaka, Kimi Araki, Toru Imamura, Masaki Ohmuraya, Minoru Tanaka, Hiroyasu Nakano
Summary: This study found that Fgf18 expression is increased in models of chronic liver fibrosis, and deleting Fgf18 can alleviate liver fibrosis. Mechanistically, overexpression of Fgf18 promotes the proliferation of HSCs, and FGF18 expression is correlated with the expression of profibrotic genes.
NATURE COMMUNICATIONS
(2023)
Review
Immunology
Takaharu Katagiri, Hideto Kameda, Hiroyasu Nakano, Soh Yamazaki
Summary: JunB is a crucial regulator in Th2 and Treg cells, modulating the expression of IL-4 and IL-2 respectively. It is also involved in regulating Th17-related genes, playing a key role in T cell differentiation and proliferation.
IMMUNOLOGICAL MEDICINE
(2021)