BMC Pulmonary Medicine
·
2024
·Vol. 24
·期 1
·1-16
·
IF 2.6
Sun Lili,Liu Lihua,Liang Dongxue,Liu Linlin
Pulmonary hypertension (PH) is a chronic pulmonary vascular disease and causes massive deaths. Here, we intended to investigate the function and mechanism of SOCS5 in PH. We engineered a hypoxia-induced PH model in mice. HE staining were implemented to evaluate pathological alterations in the lung tissues. The potential mechanism of SOCS5 in regulating hypoxia-induced pulmonary artery smooth muscle cell (PASMC) function was explored in vitro. RT-qPCR and western blot revealed that the level of SOCS5 was decreased both in PH mice and hypoxia-induced HPASMCs. Functional assays were performed for confirming the role of SOCS5 in modulating the cell phenotype and JAK2/STAT3 pathway in HPASMCs. Results revealed that overexpression of SOCS5 suppressed proliferation, migration and contraction of HPASMCs and negatively regulated the JAK2/STAT3 signaling pathway in HPASMCs under hypoxia in vitro, while knockdown of SOCS5 accelerated it. As evidenced by mechanism studies, SOCS5 was targeted and regulated by miR-155-5p, hence affecting on HPASMC proliferation, migration and contraction. These outcomes indicated that the decreased level of SOCS5 in hypoxia-induced HPASMCs promoted the cell proliferation, cell migration, and cell contraction through activating JAK2/STAT3 signaling pathway. Moreover, SOCS5 was targeted by miR-155-5p. All in all, our work hinted that miR-155-5p/SOCS5/JAK2/STAT3 axis played a crucial part in PH.
研究领域:
心血管疾病
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分子生物学
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细胞生物学
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病理生理学
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产品关联
DOI
PubMed
高影响因子
Experimental and Therapeutic Medicine
·
2021
·Vol. 22
·期 2
·1-11
·
IF 2.447
Jingli Zhang,Lingling Zhu,Hong Shi,Huizhe Zheng
Previous studies have demonstrated that microRNAs (miRNAs/miRs) serve a vital role in the pathogenesis of Sjögren's syndrome (SS). The present study aimed to investigate the role of miR‑155‑5p in SS and determine its underlying molecular mechanism. An inflammatory lesion model was established by stimulating salivary gland epithelial cells (SGECs) with interferon‑γ (IFN‑γ). The apoptosis of SGECs was measured by using flow cytometry. Levels of proinflammatory factors were detected by reverse transcription‑quantitative PCR and ELISA, respectively. Immunofluorescence was used for p65 staining. Dual‑luciferase reporter assay was performed to verify the interaction between miR‑155‑5p and arrestin β2 (ARRB2). The protein levels in the NF‑κB signaling pathway were assessed by western blotting. The results of the present study demonstrated that treatment with IFN‑γ increased miR‑155‑5p expression, in addition to inducing apoptosis and inflammation in SGECs. Furthermore, overexpression of miR‑155‑5p promoted IFN‑γ‑induced apoptosis and inflammation in SGECs. Overexpression of miR‑155‑5p also increased Bax protein expression, enzyme activities of caspase 3 and caspase 9, release of inflammatory cytokines interleukin‑6 and tumor necrosis factor‑α, and decreased Bcl‑2 protein expression in IFN‑γ‑treated SGECs. By contrast, all of the effects aforementioned were reversed following miR‑155‑5p knockdown. These results demonstrated that miR‑155‑5p activated the NF‑κB signaling pathway, where treatment with the NF‑κB inhibitor, pyrrolidine dithiocarbamate, reversed the effects of miR‑155‑5p overexpression on the inflammatory factors in IFN‑γ‑induced SGECs. miR‑155‑5p was demonstrated to target ARRB2 and negatively regulated its expression levels, such that overexpression of ARRB2 reversed the effects of miR‑155‑5p overexpression on the inflammatory response, apoptosis and the NF‑κB signaling pathway in IFN‑γ‑treated SGECs. Collectively, results from the present study suggest that miR‑155‑5p may activate the NF‑κB signaling pathway by negatively regulating ARRB2 to promote salivary gland damage during SS pathogenesis. This suggests that miR‑155‑5p may serve to be a potential target for the treatment of SS.
研究领域:
免疫学
·
分子生物学
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细胞生物学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULAR MEDICINE
·
2023
·Vol. 29
·期 1
·1-17
·
IF 5.7
Feng Yuqing,Lu Jinfang,Peng Xujun,Ge Yanni,Zhang Ran,Li Huiling
Background Retinal ganglion cells (RGCs) apoptosis is a vital manifestation of retinal ischemia/reperfusion (I/R) injury, yet the underlying mechanisms are not well understood. The contribution of long noncoding RNAs (lncRNAs) to this cellular process is currently being explored. Based on a lncRNA chip assay, we aimed to investigate the role of lncRNA uc007nnj.1 in the pathological process of ischemia-induced RGCs apoptosis.Methods Hank’s balanced salt solution containing 10 µM antimycin A and 2 µM calcium ionophore for 2 h to construct an ischemic model in RGCs, and elevation of intraocular pressure to 120 mm Hg for 1 h was used to construct a mouse model of retinal I/R injury.Results In this study, lncRNA uc007nnj.1 was highly upregulated in response to I/R injury in RGCs and mouse retinas. In addition, lncRNA uc007nnj.1 knockdown reduced retinal neuronal cell apoptosis in vitro and in vivo and significantly improved retinal function.DiscussionMechanistically, the results demonstrated that lncRNA uc007nnj.1 acts as ceRNA competitively binding miR-155-5p, thereby enhancing the expression levels of Tle4, thus aggravating ischemia-related apoptosis in RGCs.Conclusion sFinally, our study identifies the lncRNA uc007nnj.1/miR-155-5p/Tle4 axis as a potential target for the prevention of I/R-induced retinal neuronal death.
研究领域:
神经科学
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分子生物学
·
眼科
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PATHOLOGY RESEARCH AND PRACTICE
·
2021
·
IF 3.25
Yang Yang,Guoying Zhang,Jian Li,Rui Gong,Yingbao Wang,Yang Qin,Qinrong Ping,Libing Hu
Background Increasing evidences have proved that long noncoding RNAs (lncRNAs) regulate the occurrence of bladder cancer (BC) and participate in various pathophysiology processes. However, little is unknown about the role of lncRNAs in drug resistance of BC cells. In this study, we explored the role of non-coding RNA activated by DNA damage (NORAD) in the gemcitabine (GEM) resistant of BC cells and explored its potential mechanism. Methods Real-time quantitative PCR (RT-qPCR) was used to detect the expression of NORAD and miR-155–5p of BC cells. Cell counting kit-8 (CCK-8) and Western blot were used to detect cell inhibition rate and the expression of WEE1 G2 checkpoint kinase (WEE1), P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1). Flow cytometry detected cell cycle and apoptosis . Dual luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay were used to confirm the targeting relationship between miR-155–5p, NORAD and WEE1. The xenograft model was used to observe the function of NORAD in vivo. immunohistochemistry (IHC) assay was used to detect the expression of WEE1, caspase-3 and Ki67 in tumor tissues. Results NORAD highly expressed in GEM-resistant BC cell lines . Knockdown of NORAD significantly inhibited the proliferation of T24/GEM cells, the expression of drug-resistant proteins P-gp and MRP1, inhibit the G0/G1 phase of cells, and induce cell apoptosis. Knockdown of NORAD reversed the promotion effect of miR-155–5p on WEE1 expression and promoted the sensitivity of T24/GEM cells to GEM. In vivo , knockdown of NORAD inhibited the tumor growth, and enhanced the GEM-sensitivity in mice. Conclusion These data highlight the potential of NORAD acts as a therapeutic target for BC GEM resistance. It revealed the vital roles of NORAD/miR-155–5p/WEE1 axis in GEM resistant BC cells, providing a novel therapeutic strategy for BC.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
CURRENT NEUROVASCULAR RESEARCH
·
2023
·Vol. 20
·期 4
·480-492
·
IF 2.1
Li Xuejing,Wang Ying,Zhou Xiang,Wang Hui,Xu Jiang
Background: Increasing evidence shows that electroacupuncture pretreatment (EP) plays a crucial role in cerebral ischemia-reperfusion (I/R) injury, and cerebral I/R injury is the most serious complication of ischemic stroke treatment. The role of miR-155-5p in cerebral I/R injury has
been studied, but the regulation of EP on miR-155-5p has not been reported.Methods: The middle cerebral artery occlusion (MCAO) mice were used to investigate the role of EP in cerebral I/R injury. Longa and modified neurological severity scores (mNSS) were used to evaluate neurological
impairment. HE staining and TUNEL staining were used to evaluate brain injury. The expressions of miR-155-5p, Yin Yang 1 (YY1) and p53 were detected by qRT-PCR. The expressions of related proteins were detected by western blot. The binding of YY1 to miR- 155-5p was verified by dual-luciferase
reporter assay and chromatin immunoprecipitation (ChIP) assay. Mice brain microvascular endothelial cells (BMECs) were isolated and cultured for in vitro experiments. Oxygen-glucose deprivation/reoxygenation (OGD/R) was used to verify the role of YY1, p53 and miR-155-5p in cerebral I/R injury
in vitro.Results: MCAO modeling induced brain injury, apoptosis, and increased levels of miR-155-5p, YY1, and p53. EP markedly alleviated brain injury and reduced levels of miR-155-5p, p53, and YY1. miR-155 agomir markedly increased the expression of miR-155-5p and p53. miR-155 antagomir
decreased the levels of miR-155-5p and p53. Dual-luciferase reporter and ChIP assay verified that YY1 regulated miR-155-5p expression. YY1 shNRA greatly decreased miR-155-5p and p53. Inhibition of p53 decreased miR-155-5p expression. Both miR-155-5p inhibitor and YY1 shRNA promoted proliferation,
inhibited apoptosis, and decreased levels of ICAM-1 and Eselectin of OGD/R-treated BMECs. Inhibition of p53 strengthened the effect of miR-155-5p inhibitor and YY1 shNRA on BMECs.Conclusion: Electroacupuncture pretreatment alleviates cerebral ischemia-reperfusion injury by regulating the
YY1/p53/miR-155-5p axis.
研究领域:
神经科学
·
分子生物学
·
针灸
·
脑血管疾病
✓ 已验证
DOI
PubMed
高影响因子
Analytical Methods
·
2024
·
IF 2.7
Xiaoxia Lu,Wenlong Lu,Dong Hua
In the study, a novel surface-enhanced Raman scattering (SERS)-lateral flow assay (LFA) tray for the real-time detection of pyroptosis-associated miR-155-5p in breast cancer cells was established and validated. The SERS probe modified with monoclonal antibodies and functionalized HP1@5-FAM was first synthesized. When miR-155-5p was present, HP1@5-FAM on the SERS probe specifically recognized target miRNAs and hybridized with them, resulting in HP2 on the T line only capturing some SERS probes that were not bound to miR-155-5p. The T line appeared as a light orange band or there was no color change, and the corresponding Raman detection result showed a weak or insignificant Raman signal. The SERS probe showed high selectivity, satisfactory stability, and excellent reproducibility, and the limit of detection (LOD) for miR-155-5p was 7.26 aM. Finally, the proposed SERS-LFA tray was applied to detect miR-155-5p in MBA-MD-468 cells that underwent varying degrees of pyroptosis, and the detection results of SERS were consistent with those of the conventional real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) assay. The study demonstrated that the SERS-LFA tray was a convenient and ultrasensitive method for miR-155-5p real-time detection, which could provide more detailed information for pyroptosis and be of potential value in guiding the treatment of breast cancer.
研究领域:
癌症生物学
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分子生物学
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生物医学工程
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分析化学
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产品关联
DOI
PubMed
高影响因子
Frontiers in Oncology
·
2021
·
IF 6.244
Yang Jianru,Jia Yang,Wang Bing,Yang Shengrong,Du Kun,Luo Yujie,Li Yunhe,Zhu Bing
Background: The effects of up-regulated CircCHST15 on lung cancer remained unclear. In this study, the role of CircCHST15 in lung cancer was investigated.Methods: Dual-luciferase reporter verified the bioinformatics prediction that CircCHST15 targeted miR-155-5p and miR-194-5p. The correlation between CircCHST15 and PD-L1 was analyzed by Pearson analysis. CCK-8 and colony formation was performed to determine the viability and proliferation of lung cancer cells. After the lung cancer (subcutaneous-xenotransplant) model was established in mice, the T cell subtype and related cytokines in mouse tumor tissues were detected by flow cytometry and ELISA. Moreover, the expressions of CircCHST15, miR-155-5p, miR-194-5p, immune-related, and proliferation-related factors of the lung cancer cells or mice tumor tissues were detected by immunohistochemistry, RT-qPCR, or Western blot.Results: CircCHST15 and PD-L1 were high-expressed in lung cancer, and the two was positively correlated. CircCHST15 targeted miR-155-5p and miR-194-5p, the later further targeted PD-L1. Lung cancer cell viability and proliferation were increased by miR-155-5p and inhibited by miR-194-5p. CircCHST15 located in the cytoplasm promoted tumor growth, down-regulated the expressions of miR-155-5p and miR-194-5p, and up-regulated the expressions of PD-L1, Ki-67, PCNA, CCL17, CCL22, IFN-γ, TNF-β, and IL-10. Also, CircCHST15 decreased the CD8+ cells in mouse blood and tumor, but increased the Tregs in mouse tumor. PD-L1 inhibitor showed an opposite effect to CircCHST15 on mouse tumors.Conclusion: CircCHST15 sponged miR-155-5p and miR-194-5p to promote the PD-L1-mediated immune escape of lung cancer cells.
研究领域:
肿瘤学
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分子生物学
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免疫学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION
·
2020
·
IF 1.466
Zhan Wang,Rui Chen,Zheming Xu,Wei Ru,Hongjuan Tian,Fan Yang,Chang Tao
Protection against renal fibrosis is important for the management of obstructive nephropathy. We researched the roles and possible mechanism of miR-155-5p in renal interstitial fibrosis, which may provide a potential endogenous target for renal interstitial fibrosis in obstructive nephropathy. Herein, NRK-49F cells were transfected with miR-155-5p mimic, miR-155-5p inhibitor, SIRT1 plasmid and/or SIRT1 siRNA. The unilateral ureteral obstruction (UUO) model was built with male C57 black mice and administrated with SRT1720 by tail vein injection. Levels of miR-155-5p, SIRT1 and relative proteins (TGF-β1, α-SMA, Collage I and fibronectin) in NRK-49F cells or mice kidney tissues were measured with quantitative reverse transcription polymerase chain reaction or Western blot. The target gene of miR-155-5p was analyzed through TargetScan and dual-luciferase reporter assay. Mice kidney tissue was stained with Masson trichrome. It was found that miR-155-5p overexpression promoted the expressions of fibroblast related proteins expression and inhibited the SIRT1 expression in NRK-49F cells, while miR-155-5p silencing had an opposite effect. SIRT1 can bind with miR-155-5p. MiR-155-5p inhibited the level of SIRT1. Fibroblast related proteins were up-regulated by miR-155-5p and down-regulated by SIRT1 in NRK-49F cells, while the up-regulatory effect of miR-155-5p was reversed by SIRT1. MiR-155-5p expression was up-regulated and SIRT1 expression was down-regulated in the kidney tissue of UUO mice. SRT1720 attenuated the fiber deposition, up-regulated SIRT1 level and down-regulated the levels of fibroblast related proteins in UUO model mice. To conclude, miR-155-5p promotes renal interstitial fibrosis in obstructive nephropathy via inhibiting SIRT1 signaling pathway.
研究领域:
肾病学
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分子生物学
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病理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2020
·
IF 4.486
Runxiao Lv,Lili Du,Fenghua Zhou,Xiangnan Yuan,Xueyong Liu,Lixin Zhang
Parkinson’s disease (PD) is the second most common neurodegenerative disorder mainly occurring in the elderly. MicroRNA-155-5p (miR-155-5p) plays a vital role in neurodegenerative disease and has been reported to be regulated by rosmarinic acid (RA). In our previous study, it was found that RA could improve motor function and alleviate inflammatory responses in a mice model of PD. This study aimed to investigate the role of miR-155-5p in RA-treated PD mice. The PD mice model was established by injecting mice with N-methyl-4-phenyl-l,2,3,6-tetrahydropyridine (MPTP) and treated with RA or/and miR-155-5p agomir. The effects of miR-155-5p agomir on motor function, microglial activation, inflammation, apoptosis, and oxidative stress were analyzed by performing a behavioral test, ionized calcium-binding adapter molecule 1 staining, quantitative real-time PCR, Western blot, enzyme-linked immunosorbent assay, tyrosine hydroxylase (TH)-terminal dUTP nick end labeling double staining, TH-cleaved-caspase 3 double staining, and assessment of antioxidative parameters in RA-treated PD mice. The interaction between miR-155-5p and suppressor of cytokine signaling 1/nuclear factor erythroid 2-related factor 2 was validated using dual-luciferase reporter assay. MiR-155-5p up-regulation inhibited the alleviation of motor deficits caused by RA in PD mice, as evidenced by increasing descending time, decreasing limb movement score, increasing the time crossing the beam, and decreasing the times of front limb use. MiR-155-5p up-regulation could elevate microglial activation, inflammation, apoptosis, and oxidative stress in RA-treated PD mice. In conclusion, RA was able to alleviate PD by regulating miR-155-5p, suggesting that miR-155-5p could be used as a therapeutic target for PD treatment.
研究领域:
神经科学
·
药理学
·
分子生物学
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2024
·
IF 10
Junjun Yang,Xiaoyuan Gong,Tao Li,Zengzilu Xia,Rui He,Xiongbo Song,Xin Wang,Jiangyi Wu,Jiajia Chen,Fangzheng Wang,Ran Xiong,Yangjing Lin,Guangxing Chen,Liu Yang,Kaiyong Cai
In this study, the regulatory role and mechanisms of tantalum (Ta) particles in the bone tissue microenvironment are explored. Ta particle deposition occurs in both clinical samples and animal tissues following porous Ta implantation. Unlike titanium (Ti) particles promoting M1 macrophage (Mϕ) polarization, Ta particles regulating calcium signaling pathways and promoting M2 Mϕ polarization. Ta-induced M2 Mϕ enhances bone marrow-derived mesenchymal stem cells (BMSCs) proliferation, migration, and osteogenic differentiation through exosomes (Exo) by upregulating miR-378a-3p/miR-221-5p and downregulating miR-155-5p/miR-212-5p. Ta particles suppress the pro-inflammatory and bone resorption effects of Ti particles in vivo and in vitro. In a rat femoral condyle bone defect model, artificial bone loaded with Ta particles promotes endogenous Mϕ polarization toward M2 differentiation at the defect site, accelerating bone repair. In conclusion, Ta particles modulate Mϕ polarization toward M2 and influence BMSCs osteogenic capacity through Exo secreted by M2 Mϕ, providing insights for potential bone repair applications.
研究领域:
生物材料
·
免疫学
·
骨生物学
·
干细胞研究
·
再生医学
✓ 已验证
DOI
高影响因子
Redox Biology
·
2025
·
IF 11.9
Dan Liu,Hui Yu,Zhicun Liu,Le Wang,Dawo Liu,Xiangyu Cao
Acrolein is a significant high priority hazardous air pollutant. This research explore the relationship of acrolein-induced ferroptosis with the pathogenesis of lung injury by combining cellular, transcriptome, and animal-level studies. The results in vivo and in vitro models indicated that a total of 18,868 differenced lncRNAs and 15,639 differenced mRNAs were obtained after acrolein exposure. After screening, 636 lncRNAs and 214 mRNAs were obviously different of the acrolein injured group with the control group. Differential genes were mainly enriched in the iron ion binding, tissue homeostasis, etc. Among them, lncRNA MIR155HG significantly responded to the toxic effects of acrolein, the knockdown of lncRNA MIR155HG could inhibit miR-155-5p expression, promote CD200R1 expression, and improve cell viability. Furthermore, it effectively inhibited acrolein-induced the activation of ferroptosis pathway in BEAS-2B cells and lung tissue, indicating that lncRNA MIR155HG might be a potential new target for the inhibition of acrolein toxicity. LncRNA-MIR155HG/miR-155-5p/CD200R1 axis played an significant role in the lung injury, and induced ferroptosis by regulating the Nrf2/SLC7A11/GPX4 pathway. This study is the first to reveal that acrolein exposure significantly affected lncRNA and mRNA expression in BEAS-2B cells, and found that lncRNA MIR155HG effectively regulated acrolein-induced ferroptosis pathway, providing novel insights for the treatment of lung injury.
研究领域:
毒理学
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分子生物学
·
环境卫生
·
呼吸系统疾病
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基因组学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）