RESPIRATORY RESEARCH
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2026
·
IF 5
Zhang Jia,Liu Jin,Chen Yuqian,Chen Huan,Meng Yihan,Wang Yan,Qiu Yuanjie,Hu Huizhong,Shi Wenhua,Li Manxiang,Li Man-xiang
Background Galactose lectin-3 (Gal-3) has been shown to promote the progression of pulmonary arterial hypertension (PAH), yet the intricate molecular mechanisms are still unclear. Methods Primary cultured rat pulmonary arterial smooth muscle cells (PASMCs) and PAH rats were used in this study. Protein phosphorylation and expression levels were identified using Western blotting, while mRNA level was quantified through qRT-PCR. Hemodynamic measurements, hematoxylin-eosin and immunohistochemistry staining were employed to assess the PAH progression. Results Yes-associated protein 1 (YAP1) mediated Gal-3/toll-like receptor 4 (TLR4)-induced PDZ-binding kinase (PBK) upregulation. Furthermore, polo-like kinase 1 (PLK1)/cyclin-dependent kinase 1 (CDK1) mediated Gal-3/TLR4-induced PBK phosphorylation. Activated PBK further phosphorylated protein regulator of cytokinesis 1 (PRC1), which ultimately led to PASMC proliferation. In monocrotaline-induced PAH rat models, inhibition of Gal-3, TLR4, YAP1, CDK1 or silencing of PLK1, PBK, PRC1 attenuated PAH progression. Conclusion Our study presents novel evidence that Gal-3 promotes PASMC proliferation and pulmonary vascular remodeling by activating PBK/PRC1 through the TLR4/YAP1 and TLR4/PLK1/CDK1 signaling pathways, suggesting that this signaling pathway might be a promising target for the treatment of PAH.
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DOI
PubMed
高影响因子
Cell Stem Cell
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2017
·
IF 23.394
Huanhuan Li,Ping Lai,Jinping Jia,Yawei Song,Qing Xia,Kaimeng Huang,Na He,Wangfang Ping,Jiayu Chen,Zhongzhou Yang,Jiao Li,Mingze Yao,Xiaotao Dong,Jicheng Zhao,Chunhui Hou,Miguel A. Esteban,Shaorong Gao,Duanqing Pei,Andrew P. Hutchins,Hongjie Yao
Summary RNA-binding proteins (RBPs), in addition to their functions in cellular homeostasis, play important roles in lineage specification and maintaining cellular identity. Despite their diverse and essential functions, which touch on nearly all aspects of RNA metabolism, the roles of RBPs in somatic cell reprogramming are poorly understood. Here we show that the DEAD-box RBP DDX5 inhibits reprogramming by repressing the expression and function of the non-canonical polycomb complex 1 (PRC1) subunit RYBP. Disrupting Ddx5 expression improves the efficiency of iPSC generation and impedes processing of miR-125b, leading to Ryb p upregulation and suppression of lineage-specific genes via RYBP-dependent ubiquitination of H2AK119. Furthermore, RYBP is required for PRC1-independent recruitment of OCT4 to the promoter of Kdm2b , a histone demethylase gene that promotes reprogramming by reactivating endogenous pluripotency genes. Together, these results reveal important functions of DDX5 in regulating reprogramming and highlight the importance of a Ddx5-miR125b-Rybp axis in controlling cell fate.
研究领域:
分子生物学
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干细胞研究
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表观遗传学
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高影响因子
Cell Death Discovery
·
2023
·Vol. 9
·期 1
·1-16
·
IF 7
Shi Pilong,Wu Jiawei,Li Minghui,Cao Yonggang,Wu Jiabi,Ren Ping,Liu Kai,Zhou Jiajun,Sha Yuetong,Zhang Qianhui,Sun Hongli
Research suggests that ischemic glycolysis improves myocardial tolerance to anoxia and low-flow ischemia. The rate of glycolysis during ischemia reflects the severity of the injury caused by ischemia and subsequent functional recovery following reperfusion. Histone H2AK119 ubiquitination ( H2Aub ) is a common modification that is primarily associated with gene silencing. Recent studies have demonstrated that H2Aub contributes to the development of cardiovascular diseases. However, the underlying mechanism remains unclear. This study identified Hsp27 (heat shock protein 27) as a H2Aub binding protein and explored its involvement in mediating glycolysis and mitochondrial function. Functional studies revealed that inhibition of PRC1 (polycomb repressive complex 1) decreased H2Aub occupancy and promoted Hsp27 expression through inhibiting ubiquitination. Additionally, it increased glycolysis by activating the NF-κB / PFKFB3 signaling pathway during myocardial ischemia. Furthermore, Hsp27 reduced mitochondrial ROS production by chaperoning COQ9 , and suppressed ferroptosis during reperfusion. A delivery system was developed based on PCL-PEG-MAL (PPM)-PCM-SH (CWLSEAGPVVTVRALRGTGSW) to deliver PRT4165 (PRT), a potent inhibitor of PRC1 , to damaged myocardium, resulting in decreased H2Aub . These findings revealed a novel epigenetic mechanism connecting glycolysis and ferroptosis in protecting the myocardium against ischemia/reperfusion injury.
研究领域:
心血管研究
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表观遗传学
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分子生物学
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细胞生物学
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高影响因子
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