지원사업
학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
커뮤니티
연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2024.8
- 수록면
- 1,843 - 1,855 (13page)
- DOI
- 10.1038/s12276-024-01280-5
이용수
초록· 키워드
오류제보하기
Innate immune activation is critical for initiating hepatic inflammation during nonalcoholic steatohepatitis (NASH) progression. However, the mechanisms by which immunoregulatory molecules recognize lipogenic, fibrotic, and inflammatory signals remain unclear. Here, we show that high-fat diet (HFD)-induced oxidative stress activates Foxo1, YAP, and Notch1 signaling in hepatic macrophages. Macrophage Foxo1 deficiency (Foxo1M-KO) ameliorated hepatic inflammation, steatosis, and fibrosis, with reduced STING, TBK1, and NF-κB activation in HFD-challenged livers. However, Foxo1 and YAP double knockout (Foxo1/YAPM-DKO) or Foxo1 and Notch1 double knockout (Foxo1/Notch1M-DKO) promoted STING function and exacerbated HFD-induced liver injury. Interestingly, Foxo1M-KO strongly reduced TGF-β1 release from palmitic acid (PA)- and oleic acid (OA)-stimulated Kupffer cells and decreased Col1α1, CCL2, and Timp1 expression but increased MMP1 expression in primary hepatic stellate cells (HSCs) after coculture with Kupffer cells. Notably, PA and OA challenge in Kupffer cells augmented LIMD1 and LATS1 colocalization and interaction, which induced YAP nuclear translocation. Foxo1M-KO activated PGC-1α and increased nuclear YAP activity, modulating mitochondrial biogenesis. Using chromatin immunoprecipitation (ChIP) coupled with massively parallel sequencing (ChIP-Seq) and in situ RNA hybridization, we found that NICD colocalizes with YAP and targets Mb21d1 (cGAS), while YAP functions as a novel coactivator of the NICD, which is crucial for reprogramming STING function in NASH progression. These findings highlight the importance of the macrophage Foxo1–YAP–Notch1 axis as a key molecular regulator that controls lipid metabolism, inflammation, and innate immunity in NASH.
목차
등록된 정보가 없습니다.
참고문헌 (0)
참고문헌 신청함께 읽어보면 좋을 논문
논문 유사도에 따라 DBpia 가 추천하는 논문입니다. 함께 보면 좋을 연관 논문을 확인해보세요!
-
Overcoming BRAF and CDK4/6 inhibitor resistance by inhibiting MAP3K3-dependent protection against YAP lysosomal degradation
Experimental and Molecular Medicine
2024 .04
-
DNA binding partners of YAP/TAZ
BMB Reports
2018 .01
-
Roles of YAP in mediating endothelial cell junctional stability and vascular remodeling
BMB Reports
2015 .01
-
Nobiletin ameliorates hepatic ischemia and reperfusion injury through the activation of SIRT-1/FOXO3a-mediated autophagy and mitochondrial biogenesis
Experimental and Molecular Medicine
2019 .01
-
The potential role of YAP in head and neck squamous cell carcinoma
Experimental and Molecular Medicine
2020 .08
-
Clinical implications of the Hippo-YAP pathway in multiple cancer contexts
BMB Reports
2018 .01
-
YAP inactivation in estrogen receptor alpha-positive hepatocellular carcinoma with less aggressive behavior
Experimental and Molecular Medicine
2021 .06
-
YAP1 inhibits the senescence of alveolar epithelial cells by targeting Prdx3 to alleviate pulmonary fibrosis
Experimental and Molecular Medicine
2024 .07
-
Resveratrol suppresses breast cancer cell invasion by inactivating a RhoA/YAP signaling axis
Experimental and Molecular Medicine
2017 .01
-
Dishevelling Wnt and Hippo
BMB Reports
2018 .01
-
Defect of SIRT1-FoxO3a axis is associated with the production of reactive oxygen species during protein kinase CK2 downregulation-mediated cellular senescence and nematode aging
BMB Reports
2019 .01
-
Hippo-YAP/TAZ signaling in angiogenesis
BMB Reports
2018 .01
-
Regulation of Hippo signaling by actin remodeling
BMB Reports
2018 .01
-
Interacting network of Hippo, Wnt/β-catenin and Notch signaling represses liver tumor formation
BMB Reports
2017 .01
-
Deubiquitinase YOD1: the potent activator of YAP in hepatomegaly and liver cancer
BMB Reports
2017 .06
-
Inactivation of Stat3 and crosstalk of miRNA155-5p and FOXO3a contribute to the induction of IGFBP1 expression by beta-elemene in human lung cancer
Experimental and Molecular Medicine
2018 .01
-
MeCP2 inhibits ischemic neuronal injury by enhancing methylation of the FOXO3a promoter to repress the SPRY2-ZEB1 axis
Experimental and Molecular Medicine
2022 .08
-
Regulation and Regulators of the Hippo-YAP/TAZ Pathway
한국생물공학회 학술대회
2016 .10
-
SET8 suppression mediates high glucose-induced vascular endothelial inflammation via the upregulation of PTEN
Experimental and Molecular Medicine
2020 .10
-
Effect of PFKFB3 on YAP-TEAD Interaction
한국생물공학회 학술대회
2024 .09
최근 본 자료
댓글(0)
0