Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury

Chen, You-Lian1; Xie, Yin-Jing2; Liu, Zhen-Mi1; Chen, Wei-Bu2; Zhang, Ru3; Ye, Hong-Xing1; Wang, Wei4; Liu, Xue-Yan1; Chen, Huai-Sheng1

2022-12-01

10.1186/s10020-021-00425-w

MOLECULAR MEDICINE   影响因子和分区

1076-1551

1528-3658

Background Sepsis is a troublesome syndrome that can cause intestinal injury and even high mortality rates. Omega-3 fatty acids (FAs) are known to protect against intestinal damage. Accordingly, the current study set out to explore if omega-3 FAs could affect sepsis-induced intestinal injury with the involvement of the microRNA (miR)-1-3p/Notch3-Smad axis. Methods First, cecal ligation and perforation (CLP) was performed to establish septic mouse models in C57BL/6J mice, and mouse intestinal epithelial MODE-K cells were induced by lipopolysaccharide (LPS) to establish sepsis cell models. The CLP-induced septic mice or LPS-exposed cells were subjected to treatment with Omega-3 FAs and activin (Smad signaling activator), miR-1-3p inhibitor and over-expressed/short hairpin RNA (oe-/sh)-Notch3 to explore their roles in inflammation, intestinal oxidative stress and cell apoptosis. A dual-luciferase reporter gene assay was further performed to verify the regulatory relationship between miR-1-3p and Notch3. Results Omega-3 FAs inhibited CLP-induced intestinal injury and ameliorated LPS-induced intestinal epithelial cell injury by down-regulating miR-1-3p, as evidenced by decreased levels of tumor necrosis factor-alpha, interleukin-1 beta (IL-1 beta) and IL-6, in addition to diminished levels of reactive oxygen species, malondialdehyde levels and superoxide dismutase activity. Furthermore, miR-1-3p could down-regulate Notch3, which inactivated the Smad pathway. Conclusion Collectively, our findings indicated that omega-3 FAs elevate the expression of Notch3 by down-regulating miR-1-3p, and then blocking the Smad pathway to alleviate intestinal epithelial inflammation and oxidative stress injury caused by sepsis.

Omega-3 fatty acids microRNA-1-3p Notch3 Smad Sepsis Intestinal injury Inflammation Stress oxidative

SCI

英语

第一 ; 通讯

Guangdong Natural Science Foundation Project[2021A1515012119] ; Shenzhen Key Laboratory of Prevention and Treatment of Severe Infections[ZDSYS20200811142804014] ; Shenzhen Key Medical Discipline Construction Fund[SZXK045]

Biochemistry & Molecular Biology ; Cell Biology ; Research & Experimental Medicine

Biochemistry & Molecular Biology ; Cell Biology ; Medicine, Research & Experimental

WOS:000748251600001

SPRINGER

MOLECULAR BIOLOGY & GENETICS

Web of Science

1.South Univ Sci & Technol, Affiliated Hosp 1, Clin Med Coll 2, Dept Crit Care Med,Shenzhen Peoples Hosp,Jinan Un, 1017 Dongmen North Rd, Shenzhen 518020, Guangdong, Peoples R China
2.South Univ Sci & Technol, Affiliated Hosp 1, Clin Lab, Shenzhen Peoples Hosp,Jinan Univ,Clin Med Coll 2, Shenzhen 518020, Peoples R China
3.South Univ Sci & Technol, Affiliated Hosp 1, Dept Gastroenterol, Shenzhen Peoples Hosp,Jinan Univ,Clin Med Coll 2, Shenzhen 518020, Peoples R China
4.South Univ Sci & Technol, Affiliated Hosp 1, Dept Endocrinol & Metab, Shenzhen Peoples Hosp,Jinan Univ,Clin Med Coll 2, Shenzhen 518020, Peoples R China

Chen, You-Lian,Xie, Yin-Jing,Liu, Zhen-Mi,et al. Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury[J]. MOLECULAR MEDICINE,2022,28(1).

Chen, You-Lian.,Xie, Yin-Jing.,Liu, Zhen-Mi.,Chen, Wei-Bu.,Zhang, Ru.,...&Chen, Huai-Sheng.(2022).Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury.MOLECULAR MEDICINE,28(1).

Chen, You-Lian,et al."Omega-3 fatty acids impair miR-1-3p-dependent Notch3 down-regulation and alleviate sepsis-induced intestinal injury".MOLECULAR MEDICINE 28.1(2022).