JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
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2018
·Vol. 22
·期 7
·3514-3525
·
IF 4.302
Wenhui Cui,Zhihui Zhang,Panpan Zhang,Jiao Qu,Cheng Zheng,Xiaoting Mo,Wencheng Zhou,Liang Xu,Hongwei Yao,Jian Gao
Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt/β-catenin and AMP-activated protein kinase (AMPK) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt/β-catenin and AMPK modulate nuclear factor erythroid-2 related factor-2 (Nrf2)-mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase-induced airspace enlargement and cigarette smoke extract (CSE)-induced lung inflammatory responses in WT mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2 −/− mice exposed to elastase. In normal human bronchial epithelial (NHBE) cells, Wnt3a overexpression up-regulated, whereas Wnt3a knockdown further down-regulated the levels of Nrf2 and its target proteins heme oxygenase-1 (HO-1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) by CSE treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt/β-catenin pathway in mouse lungs and NHBE cells. Both elastase and CSE exposures reduced AMPK phosphorylation. A specific AMPK activator metformin increased Wnt3a, β-catenin, Nrf2 phosphorylation and activation but reduced the levels of IL-6 and IL-8 in NHBE cells and mouse lungs exposed to CSE. Furthermore, Nrf2 deficiency abolished the protection of metformin against CSE-induced increase in IL-6 and IL-8 in NHBE cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a/β-catenin and AMPK on lung inflammatory responses during the development of COPD/emphysema. These findings provide potential therapeutic targets for the intervention of COPD/emphysema.
研究领域:
医学
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分子生物学
·
药理学
✓ 已验证
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2023
·
IF 9.5
Yu Wei,Xing Yun,Yanjun Guan,Shunze Cao,Xiangling Li,Yu Wang,Haoye Meng,Yujie Liu,Qi Quan,Min Wei
Inflammation is part of the natural healing response, but persistent inflammatory events tend to contribute to pathology changes of tendon or ligament. Phenotypic switching of macrophages within the inflammatory niche is crucial for tendon healing. One viable strategy to improve the functional and biomechanical properties of ruptured tendons is to modulate the transition from inflammatory to regenerative signals during tendon regeneration at the site of injury. Here, we developed a tendon repair scaffold made of biodegradable polycaprolactone by electrospinning, which was modified to deliver Wnt3a protein and served as an implant to improve tendon healing in a rat model of Achilles tendon defect. During the in vitro study, Wnt3a protein promoted the polarization of M2 macrophages. In the in vivo experiment, Wnt3a scaffold promoted the early recruitment and counting curve of macrophages and increased the proportion of M2 macrophages. Achilles function index and mechanical properties showed that the implantation effect of the Wnt3a group was better than that of the control group. We believe that this type of scaffold can be used to repair tendon defects. This work highlights the beneficial role of local delivery of biological factors in directing inflammatory responses toward regenerative strategies in tendon healing.
研究领域:
生物材料
·
组织工程
·
再生医学
·
炎症生物学
·
骨科
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
·
2021
·
IF 3.575
Hongjie Wen,Zhong Chen,Yi Cui,Yongqing Xu
Osteomyelitis is one of the most challenging diseases in the field of orthopedics for its complex pathogenesis and unsatisfactory treatment. The mechanism underlying its occurrence and development is still unclear. In our previous study, we found that long non-coding RNA (lncRNA) NONHSAT009968 inhibited the ability of osteogenic differentiation in staphylococcal protein A (SPA)-treated human bone marrow mesenchymal stem cells (hBMMSCs), but the underlying mechanism remains unclear. The current study was aimed at elucidating the possible mechanism of NONHSAT009968 in regulating osteogenic differentiation and bone defect repairability of hBMMSCs under infection. It was revealed that Wnt3a played a key role in promoting osteogenic differentiation of hBMMSCs treated with SPA in vitro. In addition, NONHSAT009968 inhibited osteogenic differentiation of hBMMSCs treated with SPA via Wnt3a, both in vivo and in vitro. In sum, the results suggested that lncNONHSAT009968 inhibited osteogenic differentiation of hBMMSCs in SA-induced inflammation through Wnt3a, which may have affected the occurrence and development of osteomyelitis. This study might provide novel insights regarding osteomyelitis and infectious bone defects.
研究领域:
骨科
·
分子生物学
·
干细胞研究
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炎症
✓ 已验证
DOI
PubMed
高影响因子
Advanced Healthcare Materials
·
2023
·
IF 10
Nan Luo,Yu-Wei Deng,Jin Wen,Xiao-Chen Xu,Rui-Xue Jiang,Jing-Yu Zhan,Yu Zhang,Bing-Qiang Lu,Feng Chen,Xi Chen
Pulp exposure often leads to pulp necrosis, root fractures, and ultimate tooth loss. The repair of the exposure site with pulp capping treatment is of great significance to preserving pulp vitality, but its efficacy is impaired by the low bioactivity of capping materials and cell injuries from the local accumulation of oxidative stress. This study develops a Wnt3a-loaded hydroxyapatite nanowire@mesoporous silica (Wnt3a-HANW@MpSi) core−shell nanocomposite for pulp capping treatments. The ultralong and highly flexible hydroxyapatite nanowires provide the framework for the composites, and the mesoporous silica shell endows the composite with the capacity of efficiently loading/releasing Wnt3a and Si ions. Under in vitro investigation, Wnt3a-HANW@MpSi not only promotes the oxidative stress resistance of dental pulp stem cells (DPSCs), enhances their migration and odontogenic differentiation, but also exhibits superior properties of angiogenesis in vitro. Revealed by the transcriptome analysis, the underlying mechanisms of odontogenic enhancement by Wnt3a-HANW@MpSi are closely related to multiple biological processes and signaling pathways toward pulp/dentin regeneration. Furthermore, an animal model of subcutaneous transplantation demonstrates the significant reinforcement of the formation of dentin–pulp complex-like tissues and blood vessels by Wnt3a-HANW@MpSi in vivo. These results indicate the promising potential of Wnt3a-HANW@MpSi in treatments of dental pulp exposure.
研究领域:
牙科学
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纳米技术
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组织工程
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干细胞生物学
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材料科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
POULTRY SCIENCE
·
2020
·
IF 2.659
Lingzi Yu,Xiaochen Xie,Keyang Jiang,Yi Hong,Zhou Zhou,Yuling Mi,Caiqiao Zhang,Jian Li
The rapid renewal and repair of the intestinal mucosa are based on intestinal stem cells ( ISC ), which are located at the crypt bottom. Paneth cells are an essential component in the crypt, which served as the niche for ISC development. However, in the chicken, how the function of Paneth cells changes during intestinal inflammation is unclear and is the key to understand the mechanism of mucosal repair. In the present study, 36 HyLine White chickens (7 d of age, n = 6) were randomly divided into 1 control and 5 lipopolysaccharide ( LPS ) injection groups. The chickens were injected (i.p.) with PBS in the control group, however, were injected (i.p.) with LPS (10 mg/kg BW) in the LPS injection groups, which would be sampled at 5 time points (1 h postinjection [ hpi ], 2 hpi, 4 hpi, 6 hpi, and 8 hpi). Results showed that tumor necrosis factor-α mRNA transcription in duodenal tissue increased gradually since 1 hpi, peaked at 4 hpi, and then reduced remarkably, indicating that 4 hpi of LPS was the early stage of intestinal inflammation. Meanwhile, the MUC2 expression in duodenal tissue was dramatically reduced since 1 hpi of LPS. The ISC marker, Lgr5 and Bmi1 , in the duodenal crypt were reduced from 1 hpi to 4 hpi and elevated later. Accordingly, the hydroethidine staining showed that the reactive oxygen species level, which drives the differentiation of ISC, in the duodenal crypt reduced obviously at 1 hpi and recovered gradually since 4 hpi. The analysis of Paneth cells showed that many swollen mitochondria appeared in Paneth cells at 4 hpi of LPS. Meanwhile, the Lysozyme transcription in the duodenal crypt was substantially decreased since 1 hpi of LPS. However, the Wnt3a and Dll1 in duodenal crypt decreased at 1 hpi of LPS, then increased gradually. In conclusion, Paneth cells were impaired at the early stage of intestinal inflammation, then recovered rapidly. Thus, the ISC activity was reduced at first and recovery soon.
研究领域:
免疫学
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胃肠病学
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动物科学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROPHARMACOLOGY
·
2025
·
IF 4.6
Xiaofan Li,Guang Shi,Wanshu Guo,Kaishu Wen,Yifei Liu,Jiayue Cheng,Meichi Liu,Yuehui Yang,Xinyu Fan
DNA methylation plays a pivotal role in neuroprotection after ischemic stroke. Oxytocin, a neuropeptide renowned for its involvement anti-inflammatory and antioxidant activities, emerges as a promising candidate for the treatment of stroke. Here, we employed a transient middle cerebral artery occlusion (tMCAO) rat model to explore the underlying mechanisms of oxytocin's therapeutic potential. We utilized the Morris Water Maze, novel object recognition, and intruder tests to assess spatial memory, cognitive memory, and social memory abilities in rats, respectively. RNA sequencing and Western blotting were employed to detect alterations in mRNA expression and protein expression levels in the hippocampus. Daily oxytocin administration (0.1 and 1.0 mg/kg, subcutaneous) for seven days significantly reduced infarct volume, restored the expression of 1100 genes, including NQO1 and HO1, and robustly promoted hippocampal neurogenesis in tMCAO rats. These effects translated into enhanced neurological function and improved learning and memory abilities. Remarkably, our findings reveal that oxytocin-induced neurogenesis is intimately linked to the activation of the Wnt3a/β-catenin signaling pathway with Nrf2 as a key downstream target. Furthermore, it is possible that oxytocin, acting through its receptors, inhibited the tMCAO-induced binding of DNMT1 to MeCP2, thereby preventing the increase in DNA methylation at the Wnt3a gene. In summary, our study implies a possible involvement of oxytocin in the activation of the DNMT1-mediated Wnt3a/β-catenin signaling pathway. It may contribute to enhancing hippocampal neurogenesis and ameliorating memory impairments in rats with ischemic stroke. This hints that oxytocin holds great promise as a potential therapeutic agent for promoting post-stroke neurogenesis.
研究领域:
神经科学
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分子生物学
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表观遗传学
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脑卒中治疗
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再生医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
·
2021
·Vol. 105
·期 23
·8823-8835
·
IF 4.813
Hong Yi,Zhou Zhou,Yu Lingzi,Jiang Keyang,Xia Jiamiao,Mi Yuling,Zhang Caiqiao,Li Jian
Previously, we found that Lactobacillus salivarius , Lactobacillus agilis , and Lactobacillus aviarius were associated with excellent egg nutrition in native chicken. Next, the optimal Lactobacillus combination is worth studying. Here, a total of 120 HyLine hens (30 hens per group contained 3 replicate cells, 10 hens/cell) in the laying peak period were randomly divided into (1) control, (2) L. salivarius + L. agilis , (3) L. salivarius + L. aviarius , and (4) L. agilis + L. aviarius groups, fed with diet only or with corresponding Lactobacilli (10 8 colony-forming units/hen/day) for 30 days. As a result, L. salivarius + L. agilis feeding could (1) improve egg-laying rate, egg weight, and albumen’s amino acid levels; (2) increase Lactobacillus abundance, decrease Escherichia coli abundance, upregulate the tryptophan metabolism pathway-related molecules, and downregulate the primary bile acid biosynthesis pathway-related molecules in intestinal contents; and (3) upregulate oxidative-phosphorylation pathway-related genes, reactive oxygen species levels, and mRNA abundance of Wnt3a , Dll1 , Lgr5 , CCDN1 , and CDK2 in the crypt. Collectively, L. salivarius + L. agilis feeding in hens could improve intestinal microflora and metabolism profile, promote crypt’s local energy metabolism and reactive oxygen species levels, and thus enhance Paneth cells and intestinal stem cells activity.
Key points
• Lactobacilli co-feeding could improve laying performance and egg nutrition. • Lactobacilli co-feeding could improve intestinal microflora and metabolism profile. • Lactobacilli co-feeding could enhance Paneth cells and intestinal stem cells activity.
研究领域:
动物科学
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微生物学
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营养学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Applied Materials & Interfaces
·
2024
·
IF 8.3
Ruichao He,Yu Wei,Shi Yan,Jiajie Chen,Yanjun Guan,Xing Xiong,Lijing Liang,Congcong Guan,Haolin Liu,Yiben Ouyang,Junli Wang,Xiwei Peng,Jianting Ye,Jinjuan Zhao,Biqin Lai,Yu Wang,Jiang Peng,Qi Quan
A pivotal approach in engineering artificial peripheral nerve sheaths encompasses the augmentation of the regenerative microenvironment via the manipulation of Schwann cells (SCs). Our investigation employed single-cell sequencing analysis to elucidate the potential functions of Schwann cells and the Wnt pathway in facilitating peripheral nerve regeneration. In vitro studies showed that activating the Wnt signaling pathway promotes the transition to repair SCs, boosting their growth, movement, and immune functions. To better understand the peripheral nerve regeneration environment, we created a polymer scaffold using ammonization and electrospinning. The Wnt3a protein was incorporated into the polycaprolactone (PCL) electrospun fiber surface. In a rat sciatic nerve defect model, the Wnt3a-modified scaffold showed better nerve repair outcomes than traditional electrospun scaffolds. After a week, the test group showed better immune regulation and angiogenesis, with a significant increase in axon growth rate observed after 3 weeks. Three-month-long animal experiments revealed notable improvements in neuroelectrophysiology, reduced organ atrophy, and enhanced sciatic nerve recovery. In this nerve defect model, Wnt3a-modified neural scaffolds achieved repair effects.
研究领域:
生物医学工程
·
神经科学
·
组织工程
·
再生医学
✓ 已验证
DOI
高影响因子
FASEB JOURNAL
·
2020
·Vol. 34
·期 3
·3583-3593
·
IF 4.966
Bu Yang,Shangfu Li,Zheng Chen,Feng Feng,Lei He,Bin Liu,Tianwei He,Xuan Wang,Ruiqiang Chen,Zihao Chen,Peigen Xie,Limin Rong
Background Amyloid β peptide (Aβ) is involved in osteoporosis, but the effects of Aβ on osteoblast and bone formation remain unclear. In this study, we investigated the effect of Aβ on bone formation. Methods An animal model of osteoporosis was established by ovariectomy in C57BL/6 mice. The mice received intraperitoneal injection of Aβ. The effect of Aβ on the osteogenic differentiation of human bone marrow stromal stem cells (hBMSCs) and differentiation of both pre-osteoblasts and pre-osteoclasts in a co-culture system were investigated. Results In the animal study, intraperitoneal injection of Aβ for 8 weeks promoted early and late osteogenic differentiation of hBMSCs. Aβ treatment significantly elevated osterix + (osteoblastic) cells but decreased TRAP + cells (osteoclasts) in the distal femur bone. In vitro study showed that Aβ treatment significantly enhanced matrix mineralization and osteogenic markers (Runx2 and osteocalcin). Aβ treatment activated Wnt/β-catenin signaling in hBMSCs. The effect of Aβ was blocked by DKK1 (a Wnt/β-catenin inhibitor) treatment. In the co-culture system, Aβ treatment significantly increased the ALP activities of MC3T3-E1 cells (pre-osteoblasts) but reduced the TRAP + RAW264.7 cells (pre-osteoclasts). Aβ treatment upregulated TCF1 and OPG proteins in MC3T3-E1 cells. Aβ treatment upregulated IκB-α but downregulated NFATc1protein in RAW264.7 cells. These effects were blocked by XAV-939 (a Wnt signaling antagonist), and then rescued by additional Wnt3a (a Wnt agonist). Conclusion Aβ treatment simultaneously promoted osteogenic differentiation via Wnt/β-catenin signaling, and inhibited osteoclasts differentiation via the OPG/RANKL/RANK system, suggesting Aβ is a positive regulator of osteoblast differentiation and bone formation.
研究领域:
生物学
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医学
·
细胞生物学
·
分子生物学
✓ 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）