Experimental and Therapeutic Medicine
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2024
·Vol. 28
·期 3
·1-11
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IF 2.4
Wenxian Tu,Meina Feng,Qin Zhou,Yunfeng Wang,Mingye Wan,Danqun Gong,Jin Li,Yuanmin Du
Evidence has shown that microRNAs (miRNAs/
miRs) play key roles in biological functions of vascular smooth muscle cells (VSMCs). However, the role of miR‑374a in VSMCs remains to be elucidated. The present study aimed to explore the influence of miR‑374a on VSMCs and its molecular mechanism. The expression level of miR‑374a was measured by reverse transcription‑quantitative (RT‑q) PCR. MTT and Transwell assay were employed to assess the role of miR‑374a in proliferation and migration of VSMCs. To order to determine miR‑374a targets, a dual‑luciferase reporter assay was conducted, which was further verified by rescue experiments. Chromatin Immunoprecipitation Assay and JASPAR databases were applied to explore the regulatory association between GATA binding protein 2 (GATA2) and miR‑374a. Western blotting or RT‑qPCR were employed to detect the protein expression levels of GATA2 or RAR‑related orphan receptor A (RORA). The present study found that miR‑374a was elevated in VSMCs following treatment with platelet‑derived growth factor‑BB (PDGF‑BB) compared with that in control group. In addition, the results demonstrated that a higher expression of a miR‑374a could promote proliferation and migration of VSMCs while miR‑374a inhibitor suppressed the PDGF‑BB‑induced proliferation and migration of VSMCs in vitro. Furthermore, circTADA2A bound to miR‑374a and then upregulated RORA expression, which resulted in inhibition in VSMCs proliferation and migration. On the other hand, the result indicated that GATA2 overexpression could augment the proliferation, migration of PDGF‑bb‑induced VSMCs, which could be rescued by miR‑374a inhibitor. The findings suggested that the GATA2/circTADA2A‑miR‑374a axis promoted the proliferation and migration of VSMCs by targeting RORA, which were closely related to atherosclerosis (AS). Thus the results might offer a new therapeutic target for AS.
研究领域:
分子生物学
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心血管疾病
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细胞生物学
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DOI
PubMed
高影响因子
PLOS BIOLOGY
·
2026
·Vol. 24
·期 3
·e3003676
·
IF 6.9
Jia Lv,Mengjing Wang,Changzhi Shi,Yanwei Wang,Yihao Zhang,Chang Gao,Tian-Qi Bi,Jing Yang,Youdong Xu,Qunan Wang,Hua Wang,De-Xiang Xu,Mingliang Fang,Yichao Huang
Humans are increasingly exposed to "eco-friendly" biodegradable microplastic pollution, whose usage in packaging and medical applications is growing exponentially. The bioplastic polylactic acid (PLA) has recently been demonstrated to release large quantities of oligomeric lactic acid (OLA) nanoplastics causing adverse health effects. No research has reported on intrauterine biodistribution of OLA, and how gestational exposure may impact on early development of the fetus. Here, we reveal that OLA plastics can readily breach the placental barrier and accumulate in various fetal organs in a mouse model. Gestational exposure to environmentally relevant dose of OLA impairs vasculature development, causing intrauterine growth restriction in the pups. Mechanistically, OLA causes blockage of the vascular endothelial growth factor pathway and abnormal physiological development of placenta, which is mediated by the obstruction of transcription factor GATA2 translocation into the nucleus. This study highlights the potential developmental health effect of oligomer nanoparticles released from biodegradable PLA plastic.
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PubMed
高影响因子
Cell Reports Medicine
·
2022
·
IF 16.988
Zemin Hou,Shengsong Huang,Zejie Mei,Longlong Chen,Jiacheng Guo,Yuanyuan Gao,Qian Zhuang,Xuebin Zhang,Qilong Tan,Tao Yang,Ying Liu,Yongnan Chi,Lifengrong Qi,Ting Jiang,Xuefeng Shao,Yan Wu,Xiaojun Xu,Jun Qin,Ruobing Ren,Huiru Tang,Denglong Wu,Zhenfei Li
Summary Prostate cancer continuously progresses following deprivation of circulating androgens originating from the testis and adrenal glands, indicating the existence of oncometabolites beyond androgens. In this study, mass-spectrometry-based screening of clinical specimens and a retrospective analysis on the clinical data of prostate cancer patients indicate the potential oncogenic effects of progesterone in patients. High doses of progesterone activate canonical and non-canonical androgen receptor (AR) target genes. Physiological levels of progesterone facilitate cell proliferation via GATA2. Inhibitors of 3β-hydroxysteroid dehydrogenase 1 (3βHSD1) has been discovered and shown to suppress the generation of progesterone, eliminating its transient and accumulating oncogenic effects. An increase in progesterone is associated with poor clinical outcomes in patients and may be used as a predictive biomarker. Overall, we demonstrate that progesterone acts as an oncogenic hormone in prostate cancer, and strategies to eliminate its oncogenic effects may benefit prostate cancer patients.
研究领域:
肿瘤学
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内分泌学
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分子生物学
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DOI
PubMed
高影响因子
iScience
·
2023
·
IF 5.8
Yao Li,Zi-Yu Liang,Hai-Lin Wang
Summary Red blood cells supply the oxygen required for all human cells and are in demand for emerging blood-loss therapy. Here we identified N6-methyl-2′-deoxyadenosine (6mdA) as an agonist that promotes the hyperproliferation of burst-forming unit erythroid (BFU-E) progenitor cells. In addition, 6mdA represses the apoptosis of erythroid progenitor cells (EPCs). Combined use of with SCF and EPO enabled cultures of isolated BFU-E to be expanded up to 5,000-fold. Transcriptome analysis showed that 6mdA upregulates the expression of the EPC-associated factors c-Kit, Myb, and Gata2 and downregulates that of the erythroid maturation-related transcription factors Gata1, Spi1, and Klf1. Mechanistic studies suggested that 6mdA enhances and prolongs the activation of erythropoiesis-associated master gene c-Kit and its downstream signaling, leading to expansion and accumulation of EPCs. Collectively, we demonstrate that 6mdA can efficiently stimulate the EPC hyperproliferation and provide a new regenerative medicine recipe to improve ex vivo generation of red blood cells.
研究领域:
血液学
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分子生物学
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再生医学
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细胞生物学
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DOI
PubMed
高影响因子
Advanced Science
·
2025
·
IF 14.1
Zetao Heng,Min Hong,Zhaocai Zhang,Ximing Ye,Jianan Zhou,Wentao Wu,Jiabing Rong,Yinchuan Xu
Heart failure with preserved ejection fraction (HFpEF) is a prevalent complex syndrome characterized by diastolic dysfunction with limited therapeutic options. While the renin-angiotensin system (RAS) is implicated in heart failure pathogenesis, the causal contribution of angiotensinogen (AGT), the unique precursor of the RAS, to HFpEF remains undefined. Using a two-hits mouse HFpEF model (high-fat diet + L-NAME), consistent upregulation of hepatic and plasma AGT is identified in wild-type mice of both sexes. Critically, hepatocyte-specific AGT deletion directly ameliorated diastolic dysfunction in male and female HFpEF mice, whereas systemic angiotensin II blockade (losartan) failed to improve cardiac diastolic function. Mechanistically, hepatic AGT drove HFpEF through LRP2-mediated internalization in cardiac endothelial cells, suppressing the GATA2/Pim3 signaling axis, which inhibited microvascular angiogenesis and ultimately exacerbated diastolic dysfunction. To validate therapeutic potential, it is demonstrated that 18β-glycyrrhetinic acid – identified as a potent hepatic AGT inhibitor – significantly improved cardiac diastolic function in HFpEF mice. These findings establish hepatic AGT as a causal contributor to HFpEF pathogenesis and reveal its therapeutic targeting as a promising strategy.
研究领域:
心脏病学
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分子生物学
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药理学
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代谢疾病
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信号转导
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DOI
PubMed
高影响因子
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