Carbon monoxide enhance colonic epithelial restitution via FGF15 derived from colonic myofibroblasts.
Carbon monoxide (CO) has been reported to ameliorate colonic inflammation and improve experimental colitis. It is well known that mucosal restitution is important to improve colitis as well as reduction of mucosal inflammation. However, it has not been clear whether CO effects to colonic mucosal restitution or not. In general, colonic myofibroblast (MF) has been reported to play an important role of colonic epithelial cell restitution via constitutive secretion of TGF-beta. In this study, we showed CO (supplied by CO-releasing molecule; CORM) treated MF conditioned medium enhanced colonic epithelial cell (YAMC) restitution and we determined gene expression in colonic MF treated with CO using microRNA. The microRNA array suggested that miR-710 was significantly reduced in MF by CO treatment and the target gene of miR-710 is determined to fibroblast growth factor (FGF)15. The CO treated MF conditioned medium which FGF15 expression was silenced extinguished the enhancement effect of epithelial cell restitution. Our findings demonstrate that CO treatment to MF increased FGF15 expression via inhibition of miR-710 and FGF15 enhanced colonic epithelial cell restitution.
Uchiyama
Kazuhiko
K
Molecular Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine, 465 Kajiicho Hirokoji Kawaramachi Kamigyo-ku, Kyoto 602-8566, Japan.
Naito
Yuji
Y
Takagi
Tomohisa
T
Mizushima
Katsura
K
Hayashi
Natsuko
N
Harusato
Akihito
A
Hirata
Ikuhiro
I
Omatsu
Tatsushi
T
Handa
Osamu
O
Ishikawa
Takeshi
T
Yagi
Nobuaki
N
Kokura
Satoshi
S
Yoshikawa
Toshikazu
T
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D002460:Cell Line; D003106:Colon / Q000166:cytology / Q000378:metabolism / Q000502:physiology*; D017077:Culture Media, Conditioned / Q000494:pharmacology; D005346:Fibroblast Growth Factors / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology; D014945:Wound Healing
D017077:Culture Media, Conditioned; C547709:MIRN710 microRNA, mouse; D035683:MicroRNAs; D009942:Organometallic Compounds; C108526:fibroblast growth factor 15, mouse; C447082:tricarbonyldichlororuthenium (II) dimer; D005346:Fibroblast Growth Factors; D002248:Carbon Monoxide