Ryota Yamagishi, Fumitaka Kamachi, Masaru Nakamura, Shota Yamazaki, Tomonori Kamiya, Masaki Takasugi, Yi Cheng, Yoshiki Nonaka, Yoshimi Yukawa-Muto, Le Thi Thanh Thuy, Yohsuke Harada, Tatsuya Arai, Tze Mun Loo, Shin Yoshimoto, Tatsuya Ando, Masahiro Nakajima, Hayao Taguchi, Takamasa Ishikawa, Hisaya Akiba, Sachiko Miyake, Masato Kubo, Yoichiro Iwakura, Shinji Fukuda, Wei-Yu Chen, Norifumi Kawada, Alexander Rudensky, Susumu Nakae, Eiji Hara, Naoko Ohtani
Long-term senescent cells exhibit a secretome termed the senescence-associated secretory phenotype (SASP). Although the mechanisms of SASP factor induction have been intensively studied, the release mechanism and how SASP factors influence tumorigenesis in the biological context remain unclear. In this study, using a mouse model of obesity-induced hepatocellular carcinoma (HCC), we identified the release mechanism of SASP factors, which include interleukin-1β (IL-1β)- and IL-1β-dependent IL-33, from senescent hepatic stellate cells (HSCs) via gasdermin D (GSDMD) amino-terminal-mediated pore...
June 24, 2022: Science Immunology