Significant contribution of TRPC6 channel-mediated Ca2+influx to the pathogenesis of Crohn's disease fibrotic stenosis.
Intestinal fibrosis is an intractable complication of Crohn's disease (CD), and, when occurring excessively, causes severe intestinal obstruction that often necessitates surgical resection. The fibrosis is characterized by an imbalance in the turnover of extracellular matrix (ECM) components, where intestinal fibroblasts/myofibroblasts play active roles in ECM production, fibrogenesis and tissue remodeling, which eventually leads to the formation of stenotic lesions. There is however a great paucity of knowledge about how intestinal fibrosis initiates and progresses, which hampers the development of effective pharmacotherapies against CD. Recently, we explored the potential implications of transient receptor potential (TRP) channels in the pathogenesis of intestinal fibrosis, since they are known to act as cellular stress sensors/transducers affecting intracellular Ca2+homeostasis/dynamics, and are involved in a broad spectrum of cell pathophysiology including inflammation and tissue remodeling. In this review, we will place a particular emphasis on the intestinal fibroblast/myofibroblast TRPC6 channel to discuss its modulatory effects on fibrotic responses and therapeutic potential for anti-fibrotic treatment against CD-related stenosis.
Department of Physiology, Fukuoka University School of Medicine, Fukuoka 814-0180, Japan.
Lin Hai
LH
Kurahara
Keizo
K
Hiraishi
Miho
M
Sumiyoshi
Mayumi
M
Doi
Yaopeng
Y
Hu
Kunihiko
K
Aoyagi
Yuwen
Y
Jian
Ryuji
R
Inoue
D002118:Calcium / Q000378:metabolism*; D003424:Crohn Disease / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology; D005355:Fibrosis; D006801:Humans; D007415:Intestinal Obstruction / Q000209:etiology*; D007422:Intestines / Q000166:cytology / Q000473:pathology*; D058990:Molecular Targeted Therapy; D058628:Myofibroblasts / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D050052:TRPC Cation Channels / Q000502:physiology*; D000074287:TRPC6 Cation Channel; D053773:Transforming Growth Factor beta1 / Q000502:physiology
D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; D053773:Transforming Growth Factor beta1; D002118:Calcium