期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 123, 期 1, 页码 443-454出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI65831
关键词
-
资金
- William Harvey Research Foundation
- German Research Foundation (Deutsche Forschungsgemeinschaft) [NE1834/1-1]
- Emory Digestive Diseases Research Development Center [DK064399]
- [R01DK089763]
- [R01DK055679]
- [R01AI64462]
- [DK061379]
- [DK072564]
- [DK079392]
- [R01HL096796-3]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL096796] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI064462] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK061379, R01DK055679, R01DK089763, R01DK072564, R24DK064399, R01DK079392] Funding Source: NIH RePORTER
N-formyl peptide receptors (FPRs) are critical regulators of host defense in phagocytes and are also expressed in epithelia. FPR signaling and function have been extensively studied in phagocytes, yet their functional biology in epithelia is poorly understood. We describe a novel intestinal epithelial FPR signaling pathway that is activated by an endogenous FPR ligand, annexin A1 (ANXA1), and its cleavage product Ac2-26, which mediate activation of ROS by an epithelial NADPH oxidase, NOX1. We show that epithelial cell migration was regulated by this signaling cascade through oxidative inactivation of the regulatory phosphatases PTEN and PTP-PEST, with consequent activation of focal adhesion kinase (FAK) and paxillin. In vivo studies using intestinal epithelial specific Nox1(-/-IEC) and AnxA1(-/-) mice demonstrated defects in intestinal mucosal wound repair, while systemic administration of ANXA1 promoted wound recovery in a NOX1-dependent fashion. Additionally, increased ANXA1 expression was observed in the intestinal epithelium and infiltrating leukocytes in the mucosa of ulcerative colitis patients compared with normal intestinal mucosa. Our findings delineate a novel epithelial FPR1/NOX1-dependent redox signaling pathway that promotes mucosal wound repair.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据