International Journal of Experimental Pathology最新文献_第3页

Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats 无花果树多糖提取物对大鼠皮肤切除伤的抗炎和愈合作用。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-11-22 DOI: 10.1111/iep.12498

Beatriz Lima Adjafre, Iásly Costa Lima, Ana Paula Negreiros Nunes Alves, Rafael Aires Lessa, Arcelina Pacheco Cunha, Maria Gonçalves Pereira, Ana Maria Sampaio Assreuy, Mário Rogério Lima Mota

{"title":"Anti-inflammatory and healing effect of the polysaccharidic extract of Opuntia ficus-indica cladodes in cutaneous excisional wounds in rats","authors":"Beatriz Lima Adjafre, Iásly Costa Lima, Ana Paula Negreiros Nunes Alves, Rafael Aires Lessa, Arcelina Pacheco Cunha, Maria Gonçalves Pereira, Ana Maria Sampaio Assreuy, Mário Rogério Lima Mota","doi":"10.1111/iep.12498","DOIUrl":"10.1111/iep.12498","url":null,"abstract":"This study aimed to investigate the anti-inflammatory and wound healing effects of the polysaccharide extract from Opuntia ficus-indica cladodes (TPL-Ofi) using a rat cutaneous wound model. After anaesthesia, four 7-mm-diameter dorsal wounds per animal (n = 6/group for each experimental day of evaluation) were created in female Wistar rats using a surgical punch. The animals were treated topically twice daily with TPL-Ofi (0.01–1%; treated group) or sterile saline (control group) for a period of 21 days. Ulcerated tissue was collected for analysis of histological parameters (inflammation score, number of polymorphonuclear, mononuclear, fibroblast/myofibroblasts and blood vessels), immunohistochemical (fibroblast growth factor 2 [FGF-2]) and oxidative stress markers (myeloperoxidase [MPO] and glutathione [GSH]). After 21 days of treatment, body weight, net organ weight and plasma biochemical levels were measured. TPL-Ofi, containing a total carbohydrate content of 65.5% and uronic acid at 2.8%, reduced oedema on the second day and increased the nociceptive threshold on the second and third days. TPL-Ofi reduced mononuclear infiltrate on the second and MPO activity on the fifth day. TPL-Ofi increased GSH levels on the second day, as well as fibroblast/myofibroblasts counts, neoangiogenesis and FGF-2 levels on the fifth and seventh days. No changes were observed in body weight, net organ weight or toxicology assessment. Topical application of TPL-Ofi exhibited anti-inflammatory and antinociceptive effects, ultimately improving wound healing in cutaneous wounds.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"33-44"},"PeriodicalIF":3.0,"publicationDate":"2023-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats 探讨M2巨噬细胞对链脲佐菌素诱导的糖尿病大鼠实验性全层创面愈合的影响。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-11-15 DOI: 10.1111/iep.12496

Parmis Khoshnoudi, Soroush Sabiza, Mohammad Khosravi, Babak Mohamadian

{"title":"Exploring effect of M2 macrophages on experimental full-thickness wound healing in streptozotocin-induced diabetic rats","authors":"Parmis Khoshnoudi, Soroush Sabiza, Mohammad Khosravi, Babak Mohamadian","doi":"10.1111/iep.12496","DOIUrl":"10.1111/iep.12496","url":null,"abstract":"Diabetes mellitus is one of the most prevalent medical conditions, in both humans and animals. People with diabetes mellitus often experience slower than normal wound healing, making it a serious health concern. This study investigates the effect of M2 differentiated macrophages on full-thickness wound healing in white Westar rats exposed to streptozocin 70 mg/kg. A full-thickness skin defect with dimensions of 2 × 2 cm was created on the back of all the animals, and their blood sugar was simultaneously assessed. The monocytes were isolated from blood samples using the plastic adherence method and were exposed to dexamethasone (5–10 μ) for 24 h. Subsequently, they were washed with PBS and incubated in fresh cell culture medium for 5 days. The differentiated M2 cells were injected into four points of the experimental ulcers of the treatment group. Macroscopic and microscopic changes were evaluated and compared over a period of two weeks between the test and control groups. The infusion of these cells a few days after wounding enhances wound healing parameters significantly, as evidenced by an increase in germinating tissue formation, wound contraction, inflammation reduction, and collagen increase in the treated group.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"13-20"},"PeriodicalIF":3.0,"publicationDate":"2023-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134648932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Notoginsenoside R1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERα/GSK-3β/β-catenin signalling pathway 三七皂苷R1通过ERα/GSK-3β/β-catenin信号通路促进人骨髓间充质干细胞的成骨分化。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-10-30 DOI: 10.1111/iep.12494

Wei Lu, Yuanxin Shi, Minglei Qian

{"title":"Notoginsenoside R1 promotes osteogenic differentiation of human bone marrow mesenchymal stem cells via ERα/GSK-3β/β-catenin signalling pathway","authors":"Wei Lu, Yuanxin Shi, Minglei Qian","doi":"10.1111/iep.12494","DOIUrl":"10.1111/iep.12494","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 Human bone marrow mesenchymal stem cells (hBMSCs) are attractive therapeutic agents for bone tissue regeneration owing to their osteogenic differentiation potential. Notoginsenoside R1 (NGR1) is a novel phytoestrogen with diverse pharmacological activities. Here, we probed whether NGR1 has an effect on the osteogenic differentiation of hBMSCs. EdU, CCK-8 and Transwell assays were used to measure proliferation and migration of hBMSCs after treatment with different doses of NGR1. hBMSCs were treated with osteogenic differentiation induction medium for osteogenesis. Alizarin red S (ARS) and alkaline phosphatase (ALP) staining were used to measure mineralized nodule formation and ALP activity in hBMSCs, respectively. ICI 182780, an antagonist of oestrogen receptor alpha (ERα) was used to inhibit ERα expression. The results showed that NGR1 enhanced hBMSC proliferation and migration. NGR1 increased ALP activity and mineralized nodule formation as well as promoting ALP, RUNX2 and OCN expression in hBMSCs. NGR1 enhanced ERα expression and promoted GSK-3β/β-catenin signal transduction in hBMSCs. ICI 182780 reversed NGR1-mediated activation of the GSK-3β/β-catenin signalling and promoted an effect on hBMSC behaviour. Thus NGR1 promotes proliferation, migration and osteogenic differentiation of hBMSCs via the ERα/GSK-3β/β-catenin signalling pathway.\u0000 </section>\u0000 </div>","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"105 1","pages":"4-12"},"PeriodicalIF":3.0,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71412173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury 脂多糖诱导的内皮细胞损伤中线粒体稳态与屏障功能的相互作用。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-10-12 DOI: 10.1111/iep.12495

Weiwei Zhu, Xiaojing Liu, Liqing Luo, Xiao Huang, Xiaozhi Wang

{"title":"Interaction between mitochondrial homeostasis and barrier function in lipopolysaccharide-induced endothelial cell injury","authors":"Weiwei Zhu, Xiaojing Liu, Liqing Luo, Xiao Huang, Xiaozhi Wang","doi":"10.1111/iep.12495","DOIUrl":"10.1111/iep.12495","url":null,"abstract":"This study aimed to investigate the effects of mitochondrial homeostasis on lipopolysaccharide (LPS)-induced endothelial cell barrier function and the mechanisms that underlie these effects. Cells were treated with LPS or oligomycin (mitochondrial adenosine triphosphate synthase inhibitor) and the mitochondrial morphology, mitochondrial reactive oxygen species (mtROS), and mitochondrial membrane potential (ΔΨm) were evaluated. Moreover, the shedding of glycocalyx-heparan sulphate (HS), the levels of HS-specific degrading enzyme heparanase (HPA), and the expression of occludin and zonula occludens (ZO-1) of Tight Junctions (TJ)s, which are mediated by myosin light chain phosphorylation (p-MLC), were assessed. Examining the changes in mitochondrial homeostasis showed that adding heparinase III, which is an exogenous HPA, can destroy the integrity of glycocalyx. LPS simultaneously increased mitochondrial swelling, mtROS, and ΔΨm. Without oligomycin effects, HS, HPA levels, and p-MLC were found to be elevated, and the destruction of occludin and ZO-1 increased. Heparinase III not only damaged the glycocalyx by increasing HS shedding but also increased mitochondrial swelling and mtROS and decreased ΔΨm. Mitochondrial homeostasis is involved in LPS-induced endothelial cell barrier dysfunction by aggravating HPA and p-MLC levels. In turn, the integrated glycocalyx protects mitochondrial homeostasis.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"272-282"},"PeriodicalIF":3.0,"publicationDate":"2023-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12495","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41201020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model 使用小鼠流感肺炎模型对螺旋藻治疗的组织形态计量学肺密度评估。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-09-26 DOI: 10.1111/iep.12493

Floyd D. Wilson, Tahir M. Mir, Mohammad K. Ashfaq, Jin Zhang, Nirmal D. Pugh, Ikhlas A. Khan, Lanny W. Pace, Frederic J. Hoerr

{"title":"Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model","authors":"Floyd D. Wilson, Tahir M. Mir, Mohammad K. Ashfaq, Jin Zhang, Nirmal D. Pugh, Ikhlas A. Khan, Lanny W. Pace, Frederic J. Hoerr","doi":"10.1111/iep.12493","DOIUrl":"10.1111/iep.12493","url":null,"abstract":"Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 104 PFU/50 μL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of “digital pneumonia” (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (R = 0.56 and 0.53 respectively), and a strong correlation (R = 0.68) for 400-× images.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"283-291"},"PeriodicalIF":3.0,"publicationDate":"2023-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12493","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41123718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

British Society for Matrix Biology Spring Meeting 2023: Vascular Inflammation and the Extracellular Matrix 英国基质生物学学会2023年春季会议:血管炎症和细胞外基质

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-09-13 DOI: 10.1111/iep.12486

引用次数: 0

Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p 通过ATF3/CSF1轴抑制炎症和M2巨噬细胞浸润:miR-27a-3p的作用

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-08-28 DOI: 10.1111/iep.12490

Bin Zhou, Yan Xu, Li Xu, Yi Kong, Kang Li, Bolin Chen, Jia Li

{"title":"Inhibition of inflammation and infiltration of M2 macrophages in NSCLC through the ATF3/CSF1 axis: Role of miR-27a-3p","authors":"Bin Zhou, Yan Xu, Li Xu, Yi Kong, Kang Li, Bolin Chen, Jia Li","doi":"10.1111/iep.12490","DOIUrl":"10.1111/iep.12490","url":null,"abstract":"Non-small cell lung cancer (NSCLC) imposes a significant economic burden on patients and society due to its low overall cure and survival rates. Tumour-associated macrophages (TAM) affect tumour development and may be a novel therapeutic target for cancer. We collected NSCLC and tumour-adjacent tissue samples. Compared with the tumour-adjacent tissues, the Activation Transcription Factor 3 (ATF3) and Colony Stimulating Factor 1 (CSF-1) were increased in NSCLC tissues. Levels of ATF3 and CSF-1 were identified in different cell lines (HBE, A549, SPC-A-1, NCI-H1299 and NCI-H1795). Overexpression of ATF3 in A549 cells increased the expression of CD68, CD206 and CSF-1. Moreover, levels of CD206, CD163, IL-10 and TGF-β increased when A549 cells were co-cultured with M0 macrophages under the stimulation of CSF-1. Using the starbase online software prediction and dual-luciferase assays, we identified the targeting between miR-27a-3p and ATF3. Levels of ATF3, CSF-1, CD206, CD163, IL-10 and TGF-β decreased in the miR-27a mimics, and the tumour growth was slowed in the miR-27a mimics compared with the mimics NC group. Overall, the study suggested that miR-27a-3p might inhibit the ATF3/CFS1 axis, regulate the M2 polarization of macrophages and ultimately hinder the progress of NSCLC. This research might provide a new therapeutic strategy for NSCLC.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"292-303"},"PeriodicalIF":3.0,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Optimization of decellularization methods using human small intestinal submucosa for scaffold generation in regenerative medicine 人小肠粘膜下层脱细胞制备再生医学支架方法的优化。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-08-25 DOI: 10.1111/iep.12492

Shumei Mineta, Shunji Endo, Tomio Ueno

{"title":"Optimization of decellularization methods using human small intestinal submucosa for scaffold generation in regenerative medicine","authors":"Shumei Mineta, Shunji Endo, Tomio Ueno","doi":"10.1111/iep.12492","DOIUrl":"10.1111/iep.12492","url":null,"abstract":"Porcine small intestinal submucosa, despite its successful use as a scaffold in regenerative medicine, has innate biomechanical heterogeneity. In this study, we hypothesized that human small intestinal submucosa could be a viable alternative bio-scaffold. For the first time, we characterize submucosal extraction from human small intestine and examine appropriate decellularization methods. In total, 16 human small intestinal submucosal samples were obtained and decellularized using three reported methods of porcine decellularization: Abraham, Badylak, and Luo. For each method, four specimens were decellularized. The remaining four specimens were designated as non-decellularized. We measured the amount of residual DNA and growth factors in decellularized human intestinal samples. Additionally, decellularized human small intestinal submucosa was co-cultured with mouse bone marrow-derived mesenchymal stem cells to examine mesenchymal stem cell survival and proliferation. The reference value for the amount of residual DNA deemed appropriate in decellularized tissue was established as 50 ng/mg of extracellular matrix dry weight or less. Abraham's method most successfully met this criterion. Measurement of residual growth factors revealed low levels observed in samples decellularized using the Abraham and Badylak methods. Co-culture of each small intestinal submucosal sample with mouse bone marrow-derived mesenchymal stem cells confirmed viable cell survival and proliferation in samples derived using protocols by Abraham and Badylak. Abraham's method most successfully met the criteria for efficient tissue decellularization and cell viability and proliferation. Thus, we consider this method most suitable for decellularization of human small intestinal submucosa.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"313-320"},"PeriodicalIF":3.0,"publicationDate":"2023-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12492","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10071861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis 在化学诱导的小鼠结肠癌模型中，Panx1基因敲除促进肿瘤前异常隐窝灶的发展。

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-08-18 DOI: 10.1111/iep.12491

Sara Gomes Espírito Santo, Tereza Cristina Da Silva, Bruno Cogliati, Luís Fernando Barbisan, Guilherme Ribeiro Romualdo

{"title":"Panx1 knockout promotes preneoplastic aberrant crypt foci development in a chemically induced model of mouse colon carcinogenesis","authors":"Sara Gomes Espírito Santo, Tereza Cristina Da Silva, Bruno Cogliati, Luís Fernando Barbisan, Guilherme Ribeiro Romualdo","doi":"10.1111/iep.12491","DOIUrl":"10.1111/iep.12491","url":null,"abstract":"Colorectal cancer, which is the third leading cause of cancer-related deaths worldwide, is a multistep disease, featuring preneoplastic aberrant crypt foci (ACF) as the early morphological manifestation. The roles of hemichannel-forming transmembrane Pannexin 1 (Panx1) protein have not been investigated in the context of colon carcinogenesis yet, although it has contrasting roles in other cancer types. Thus, this study was conducted to examine the effects of Panx1 knockout (Panx1−/−) on the early events of chemically induced colon carcinogenesis in mouse. Wild type (WT) and Panx1−/− female C57BL6J mice were submitted to a chemically induced model of colon carcinogenesis by receiving six intraperitoneal administrations of 1,2-dimethylhydrazine (DMH) carcinogen. Animals were euthanized 8 h (week 7) or 30 weeks (week 37) after the last DMH administration in order to evaluate sub-acute colon toxicity outcomes or the burden of ACF, respectively. At week 7, Panx1 genetic ablation increased DMH-induced genotoxicity in peripheral blood cells, malondialdehyde levels in the colon, and apoptosis (cleaved caspase-3) in colonic crypts. Of note, at week 37, Panx1−/− animals showed an increase in aberrant crypts (AC), ACF mean number, and ACF multiplicity (AC per ACF) by 56%, 57% and 20%, respectively. In essence, our findings indicate that Panx1 genetic ablation promotes preneoplastic ACF development during chemically induced mouse colon carcinogenesis, and a protective role of Panx1 is postulated.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 6","pages":"304-312"},"PeriodicalIF":3.0,"publicationDate":"2023-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396749","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression 通过抑制STAT3的表达，Nek6敲低极化巨噬细胞进入促炎表型

IF 3 4区医学

International Journal of Experimental Pathology Pub Date : 2023-07-10 DOI: 10.1111/iep.12489

Xiaoyan Wu, Ke-Qiong Deng, Huan-Huan Cai, Ziyue Zeng, Jian-Lei Cao, Lin Zhang, Zhibing Lu, Wen-Lin Cheng

{"title":"Nek6 knockdown polarized macrophages into a pro-inflammatory phenotype via inhibiting STAT3 expression","authors":"Xiaoyan Wu, Ke-Qiong Deng, Huan-Huan Cai, Ziyue Zeng, Jian-Lei Cao, Lin Zhang, Zhibing Lu, Wen-Lin Cheng","doi":"10.1111/iep.12489","DOIUrl":"10.1111/iep.12489","url":null,"abstract":"Recently macrophage polarization has emerged as playing an essential role in the oathogenesis of atherosclerosis, which is the most important underlying process in many types of cardiovascular diseases. Although Nek6 has been reported to be involved in various cellular processes, the effect of Nek6 on macrophage polarization remains unknown. Macrophages exposed to lipopolysaccharide (LPS) or IL-4 were used to establish an in vitro model for the study of regulation of classically (M1) or alternatively (M2) activated macrophage. Bone marrow-derived macrophages (BMDMs) transfected with short hairpin RNA-targeting Nek6 were then in functional studies. We observed that Nek6 expression was decreased in both peritoneal macrophages (PMs) and BMDMs stimulated by LPS. This effect was seen at both mRNA and protein level. The opposite results were obtained after administration of IL-4. Macrophage-specific Nek6 knockdown significantly exacerbated pro-inflammatory M1 polarized macrophage gene expression in response to LPS challenge, but the anti-inflammatory response gene expression that is related to M2 macrophages was attenuated by Nek6 silencing followed by treatment with IL-4. Mechanistic studies exhibited that Nek6 knockdown inhibited the phosphorylated STAT3 expression that mediated the effect on macrophage polarization regulated by AdshNek6. Moreover, decreased Nek6 expression was also observed in atherosclerotic plaques. Collectively, these evidences suggested that Nek6 acts as a crucial site in macrophage polarization, and that this operates in a STAT3-dependent manner.","PeriodicalId":14157,"journal":{"name":"International Journal of Experimental Pathology","volume":"104 5","pages":"237-246"},"PeriodicalIF":3.0,"publicationDate":"2023-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/iep.12489","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10256930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0