TY - JOUR
T1 - Regenerating islet-derived protein (Reg)3β plays a crucial role in attenuation of ileitis and colitis in mice
AU - Shindo, Ryodai
AU - Katagiri, Takaharu
AU - Komazawa-Sakon, Sachiko
AU - Ohmuraya, Masaki
AU - Takeda, Wakami
AU - Nakagawa, Yoshiko
AU - Nakagata, Naomi
AU - Sakuma, Tetsushi
AU - Yamamoto, Takashi
AU - Nishiyama, Chiharu
AU - Nishina, Takashi
AU - Yamazaki, Soh
AU - Kameda, Hideto
AU - Nakano, Hiroyasu
N1 - Publisher Copyright:
© 2020 The Authors
PY - 2020/3
Y1 - 2020/3
N2 - Regenerating islet-derived protein (Reg)3β belongs to a member of the Reg family of proteins and has pleiotropic functions, including antimicrobial activity and tissue repair. However, whether Reg3β plays a protective role in the development of colitis and ileitis has not been fully investigated. We generated transgenic mice expressing a short form of cellular FLICE-inhibitory protein (cFLIPs) that promotes necroptosis, a regulated form of cell death. cFLIPs transgenic (CFLARs Tg) mice develop severe ileitis in utero. Although Reg3β is undetectable in the small intestine of wild-type embryos, its expression is aberrantly elevated in the small intestine of CFLARs Tg embryos. To test whether elevated Reg3β attenuates or exacerbates ileitis in CFLARs Tg mice, we generated a Reg3b−/− strain. Reg3b−/− mice grew to adulthood without apparent abnormalities. Deletion of Reg3b in CFLARs Tg mice exacerbated the embryonic lethality of CFLARs Tg mice. Dextran sulfate sodium-induced colitis, characterized by body weight loss and infiltration of neutrophils, was exacerbated in Reg3b−/− compared to wild-type mice. Moreover, the expression of Interleukin 6, an inflammatory cytokine and Chitinase-like 3, a marker for tissue repair macrophages was elevated in the colon of Reg3b−/− mice compared to wild-type mice after DSS treatment. Together, these results suggest that attenuation of colitis and ileitis is a result of Reg3β′s real function.
AB - Regenerating islet-derived protein (Reg)3β belongs to a member of the Reg family of proteins and has pleiotropic functions, including antimicrobial activity and tissue repair. However, whether Reg3β plays a protective role in the development of colitis and ileitis has not been fully investigated. We generated transgenic mice expressing a short form of cellular FLICE-inhibitory protein (cFLIPs) that promotes necroptosis, a regulated form of cell death. cFLIPs transgenic (CFLARs Tg) mice develop severe ileitis in utero. Although Reg3β is undetectable in the small intestine of wild-type embryos, its expression is aberrantly elevated in the small intestine of CFLARs Tg embryos. To test whether elevated Reg3β attenuates or exacerbates ileitis in CFLARs Tg mice, we generated a Reg3b−/− strain. Reg3b−/− mice grew to adulthood without apparent abnormalities. Deletion of Reg3b in CFLARs Tg mice exacerbated the embryonic lethality of CFLARs Tg mice. Dextran sulfate sodium-induced colitis, characterized by body weight loss and infiltration of neutrophils, was exacerbated in Reg3b−/− compared to wild-type mice. Moreover, the expression of Interleukin 6, an inflammatory cytokine and Chitinase-like 3, a marker for tissue repair macrophages was elevated in the colon of Reg3b−/− mice compared to wild-type mice after DSS treatment. Together, these results suggest that attenuation of colitis and ileitis is a result of Reg3β′s real function.
KW - Cellular FLICE-Inhibitory protein
KW - Colitis
KW - Dextran sulfate sodium
KW - Ileitis
KW - Regenerating islet-derived protein
UR - http://www.scopus.com/inward/record.url?scp=85078995314&partnerID=8YFLogxK
U2 - 10.1016/j.bbrep.2020.100738
DO - 10.1016/j.bbrep.2020.100738
M3 - Article
AN - SCOPUS:85078995314
SN - 2405-5808
VL - 21
JO - Biochemistry and Biophysics Reports
JF - Biochemistry and Biophysics Reports
M1 - 100738
ER -