Cellular signalling最新文献

{"title":"AIM2 promotes the progression of HNSCC via STAT1 mediated transcription and IL-17/MAPK signaling","authors":"Dong Ding ,&nbsp;Hongfei Liu ,&nbsp;Liping Zhang ,&nbsp;Guoxin Zhang ,&nbsp;Yumin Wei ,&nbsp;Wenlong Zhang ,&nbsp;Xingjiu Yang ,&nbsp;Mengyuan Li ,&nbsp;Gaofei Yin ,&nbsp;Wei Guo ,&nbsp;Xiaohong Chen ,&nbsp;Zhigang Huang ,&nbsp;Ran Gao","doi":"10.1016/j.cellsig.2024.111545","DOIUrl":"10.1016/j.cellsig.2024.111545","url":null,"abstract":"<div><div>Chronic inflammation has been recognized as one of the hallmarks of head and neck squamous cell carcinoma (HNSCC), Absent In Melanoma 2(AIM2) has emerged as important regulators of chronic inflammatory, and participated in initiation, progression of kinds of human cancers. Nonetheless, the biological functions and underlying mechanisms of AIM2 in HNSCC remain inadequately understood. Based on the bioinformatics analysis of public databases, we identified elevated AIM2 expression in HNSCC, which positively correlates with disease stage and HPV infection, thereby possessing both diagnostic and prognostic significance. Immunohistochemistry on clinical samples revealed that AIM2 expression was frequently upregulated in cancerous tissues compared to paracancerous tissues, exhibiting a significant association with Ki-67 expression. Modulating AIM2 expression in HNSCC cell lines through transfection with inhibitors or mimics demonstrated that ectopic AIM2 expression enhances cell growth, migration, tumorigenesis, and metastasis both in vitro and in vivo. A dual luciferase reporter assay indicated that the transcription factor STAT1 can bind directly to the AIM2 promoter region and activate its transcription. The STAT1 inhibitor, fludarabine, reduces AIM2 expression and subsequently diminishes cell proliferation. Mechanistically, AIM2 exerts its tumor-promoting effects through the IL-17-MAPK signaling pathway. Collectively, our data demonstrate that AIM2, transcriptionally activated by STAT1, exhibits oncogenic functions by promoting the IL-17-MAPK signaling pathway, suggesting that AIM2 may be a new intervention targets for the diagnostic and treatment of HNSCC.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111545"},"PeriodicalIF":4.4,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hypoxia regulates small extracellular vesicle biogenesis and cargo sorting through HIF-1α/HRS signaling pathway in head and neck squamous cell carcinoma","authors":"Yiman Wang ,&nbsp;Bolin Xiao ,&nbsp;Jinbang Li ,&nbsp;Mengyao Zhang ,&nbsp;Linzhou Zhang ,&nbsp;Liguo Chen ,&nbsp;Jing Zhang ,&nbsp;Gang Chen ,&nbsp;Wei Zhang","doi":"10.1016/j.cellsig.2024.111546","DOIUrl":"10.1016/j.cellsig.2024.111546","url":null,"abstract":"<div><div>Small extracellular vesicles (sEVs) act as crucial messengers that transmit biological signals in hypoxic tumor microenvironment (TME), significantly impacting cancer progression. However, the precise mechanism by which hypoxia influences sEV biogenesis remains poorly understood. In this study, we observed increased sEV secretion and alterations in cargo composition in head and neck squamous cell carcinoma (HNSCC) cells under hypoxic conditions. We found that hepatocyte growth factor–regulated tyrosine kinase substrate (HRS), a key component of the endosomal sorting complexes required for transport (ESCRT), was upregulated during hypoxia. This upregulation activated the endosomal system and reduced degradation of multivesicular bodies (MVBs). HRS depletion altered the packaging of protein cargoes such as mitochondria-related proteins into sEVs under hypoxia, and these cargoes promoted a pro-tumorigenic phenotype of macrophages. Importantly, we demonstrated that HRS is transcriptionally activated by hypoxia inducible factor-1α (HIF-1α). Spatial transcriptomics and immunohistochemistry revealed a positive correlation between HRS and HIF-1α. These findings establish a link between the hypoxic response, sEV biogenesis, and cargo packaging, enhancing our understanding of how the hypoxic TME influences sEV biogenesis in HNSCC cells.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111546"},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779613","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microtubule-Rab5 mutual-influential system screening based on gene-regulatory networks map in Rab5 RNAi eye-degeneration model","authors":"Yuyu Nan ,&nbsp;Jingjing Lin ,&nbsp;Zaiwa Wei ,&nbsp;Yufeng Yang ,&nbsp;Qinghua Li","doi":"10.1016/j.cellsig.2024.111544","DOIUrl":"10.1016/j.cellsig.2024.111544","url":null,"abstract":"<div><div>Rabs are involved in neuronal development and protrusion formation. Existing studies support the notion that manipulation or mutation of <em>Rab</em> genes could lead to functional changes in neurons. However, whether <em>Rabs</em> gene-manipulation induced <em>Drosophila</em> eye-degeneration remains unknown. By down-regulating <em>Rab5</em>, but not <em>Rab7</em>, we first constructed a compound eye injury model in <em>Drosophila</em>. As the distribution, content, and even maturation of Rab5-positive endosomes are influenced by cytoskeletal proteins, like actin or tubulin-related proteins, the existence of a bidirectional regulatory relationship between Rab5 and the cytoskeleton remains unclear and worth researching. Through complete transcriptome sequencing combined immunofluorescence testing, we confirmed that down-regulation of <em>Rab5</em> affected the increase of α-Tub84B (alternatively named TubA84B) but not γ-tubulin. Based on Weighted Gene Co-Expression Network Analysis (WGCNA) and multi-tissue screening verification, this study proposes that the apoptosis-related factors–Rab5–TubA84B have conserved regulatory functions with cooperative expression. Gene manipulation confirmed that apoptotic factors, especially rpr, strongly regulate Rab5, and may ultimately influence microtubule structure through complex routes, including the Rab5 variance and the intracellular configuration ratio of α-Tubulin to Glyceraldehyde-3-phosphate dehydrogenase.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111544"},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779632","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"METTL3-mediated SMPDL3A promotes cell growth, metastasis and immune process of hepatocellular carcinoma by regulating LRPPRC","authors":"Weixin Xu ,&nbsp;Miaomiao Tao ,&nbsp;Yeqiong Liu ,&nbsp;Jun Yan ,&nbsp;Jiali Hu ,&nbsp;Lei Wang","doi":"10.1016/j.cellsig.2024.111543","DOIUrl":"10.1016/j.cellsig.2024.111543","url":null,"abstract":"<div><h3>Background</h3><div>Methyltransferase-like protein 3 (METTL3) has been confirmed to act as a tumor promoter to regulate hepatocellular carcinoma (HCC) progression. Therefore, more roles and mechanisms of METTL3 in HCC progression deserve to be further revealed.</div></div><div><h3>Methods</h3><div>The mRNA and protein levels of METTL3, sphingomyelin phodiesterase acid-like 3 A (SMPDL3A), and leucine rich pentatricopeptide repeat containing (LRPPRC) were determined by qRT-PCR and western blot. Cell proliferation, apoptosis, invasion and migration were detected by CCK8 assay, EdU assay, flow cytometry, transwell assay and wound healing assay. HCC cells were co-cultured with phytohemagglutinin-stimulated peripheral blood mononuclear cells, cytokine-induced killer cells, or CD8 + T-cells. IFN-γ, TNF-α levels, HCC cell survival rate and CD8 + T-cell apoptosis were determined to assess cell immune process. The interaction between METTL3, SMPDL3A and LRPPRC was assessed by MeRIP assay, RIP assay, dual-luciferase reporter assay or Co-IP assay. Animal experiments were performed to evaluate the effect of METTL3 knockdown on HCC tumorigenesis and lung metastasis.</div></div><div><h3>Results</h3><div>METTL3 was upregulated in HCC tissues and cells, and its knockdown repressed HCC cell proliferation, invasion, migration, immune process and promoted apoptosis. METTL3 increased SMPDL3A mRNA stability by m6A methylation modification, and this modification could be recognized by IGF2BP1. SMPDL3A overexpression reversed the inhibitory effect of METTL3 knockdown on HCC cell growth, metastasis and immune process. SMPDL3A interacted with LRPPRC to positively regulate its expression, and LRPPRC overexpression also eliminated the regulation of SMPDL3A silencing on HCC progression. In addition, downregulation of METTL3 repressed HCC tumorigenesis and lung metastasis <em>via</em> mediating SMPDL3A/LRPPRC axis.</div></div><div><h3>Conclusion</h3><div>METTL3 accelerated HCC cell growth, metastasis and immune process by regulating SMPDL3A/LRPPRC axis, providing a potential target for HCC treatment.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111543"},"PeriodicalIF":4.4,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of concern: The emerging crosstalk between atherosclerosis-related microRNAs and Bermuda triangle of foam cells: Cholesterol influx, trafficking, and efflux.","authors":"","doi":"10.1016/j.cellsig.2024.111394","DOIUrl":"10.1016/j.cellsig.2024.111394","url":null,"abstract":"","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"124 ","pages":"111394"},"PeriodicalIF":4.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Death-associated protein kinase 1 prevents hypoxia-induced metabolic shift and pulmonary arterial smooth muscle cell proliferation in PAH","authors":"Laura-Marie Seidel ,&nbsp;Jana Thudium ,&nbsp;Caroline Smith ,&nbsp;Vandna Sapehia ,&nbsp;Natascha Sommer ,&nbsp;Magdalena Wujak ,&nbsp;Norbert Weissmann ,&nbsp;Werner Seeger ,&nbsp;Ralph T. Schermuly ,&nbsp;Tatyana Novoyatleva","doi":"10.1016/j.cellsig.2024.111527","DOIUrl":"10.1016/j.cellsig.2024.111527","url":null,"abstract":"<div><div>Pulmonary hypertension (PH) is a general term used to describe high blood pressure in the lungs from any cause. Pulmonary arterial hypertension (PAH) is a progressive, and fatal disease that causes the walls of the pulmonary arteries to tighten and stiffen. One of the major characteristics of PAH is the hyperproliferation and resistance to apoptosis of vascular cells, which trigger excessive pulmonary vascular remodeling and vasoconstriction. The death-associated protein DAP-kinase (DAPK) is a tumor suppressor and Ser/Thr protein kinase, which was previously shown to regulate the hypoxia inducible factor (HIF)-1α. Against this background, we now show that DAPK1 regulates human pulmonary arterial smooth muscle cell (hPASMC) proliferation and energy metabolism in a HIF-dependent manner. DAPK1 expression is downregulated in pulmonary vessels and PASMCs of human and experimental PH lungs. Reduced expression of DAPK1 in hypoxia and non-hypoxia PAH-PASMCs correlates with increased expression of HIF-1/2α. RNA interference-mediated depletion of DAPK1 leads to fundamental metabolic changes, including a significantly decreased rate of oxidative phosphorylation associated with enhanced expression of both HIF-1α and HIF-2α and glycolytic enzymes, as hexokinase 2 (HK2), lactate dehydrogenase A (LDHA), and an integrator between the glycolysis and citric acid cycle, pyruvate dehydrogenase kinase 1 (PDK1). DAPK1 ablation in healthy donor hPASMCs leads to an increase in proliferation, while its overexpression provides the opposite effects. Together our data indicate that DAPK1 serves as a new inhibitor of the pro-proliferative and glycolytic phenotype of PH in PASMCs acting via HIF-signaling pathway.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111527"},"PeriodicalIF":4.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the mechanism of Jianpi Lishi Jiedu Granules against postoperative recurrence of colorectal adenoma based on IL-6/JAK/STAT3 signaling pathway","authors":"Yuzhen Huang ,&nbsp;Yulu Wang ,&nbsp;Hao Wu ,&nbsp;Yan Wang ,&nbsp;Yanting Deng ,&nbsp;Yuan Chang ,&nbsp;Kunhan Su ,&nbsp;Lu Yang ,&nbsp;Weiwei Tao ,&nbsp;Wanli Liu","doi":"10.1016/j.cellsig.2024.111535","DOIUrl":"10.1016/j.cellsig.2024.111535","url":null,"abstract":"<div><div>Globally, colorectal cancer (CRC) is the primary cause of cancer-related fatalities. Our previous study demonstrated the efficacy of Jianpi Lishi Jiedu Granules (JLJG) in preventing postoperative recurrence of colorectal adenoma (CRA). Building on this foundation, the current study aims to elucidate whether the mechanism by which JLJG prevents postoperative recurrence of CRA involves the classical JAK/STAT inflammatory signaling pathway and to assess its specific impact on this pathway. Utilizing proteomics, we discerned 143 differentially expressed proteins (DEPs) regulated by JLJG, whose functional roles are intimately linked to the JAK/STAT signaling pathway. Among these, we identified key proteins such as IL-6, JAK1, JAK2, STAT3, CCND1, MYC, Bcl-XL, and SOCS3 that are regulated by JLJG and play pivotal roles in the JAK/STAT signaling cascade. Our findings indicate that the sustained activation of the IL-6/JAK/STAT3 signaling pathway is significantly associated with CRA recurrence. JLJG was found to effectively modulate the expression levels of these proteins, as well as the expression of downstream genes including BCL2, MCL1, P21, and JAK1, STAT3, thereby inhibiting the IL-6/JAK/STAT3 signaling pathway. Consequently, this study demonstrates that JLJG prevents the postoperative recurrence of CRA by inhibiting the IL-6/JAK/STAT3 signaling pathway and its negative feedback loops.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111535"},"PeriodicalIF":4.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of HIF-1α C-terminal transactivation domain promotes tubulointerstitial fibrosis through hexokinase 2-mediated metabolic reprogramming","authors":"Yao Zhang ,&nbsp;Jin-Hua Zhu ,&nbsp;Yan Zhou ,&nbsp;Zhong-Tang Li ,&nbsp;Hong Liu ,&nbsp;Rui-Xia Ma ,&nbsp;Zuo-Lin Li","doi":"10.1016/j.cellsig.2024.111531","DOIUrl":"10.1016/j.cellsig.2024.111531","url":null,"abstract":"<div><h3>Background</h3><div>The hypoxia-inducible factor-1α (HIF-1α), a master transcription factor for adaptive responses to hypoxia, possesses two transcriptional activation domains [TAD, N-terminal (NTAD) and C-terminal (CTAD)]. However, the exact effects of HIF-1α CTAD in chronic kidney disease (CKD) are poorly understood.</div></div><div><h3>Methods</h3><div>Here, two independent mouse models of hypoxia-induced CKD, including ischemia/reperfusion-induced kidney injury and unilateral ureteral obstruction-induced nephropathy, were established using HIF-1α CTAD knockout (<em>HIF-1α CTAD</em>^{<em>−/−</em>}) mice. Further, hexokinase 2 (HK2) and glycolysis pathway were modulated using genetic and pharmacological interventions, respectively.</div></div><div><h3>Results</h3><div>We found that HIF-1α CTAD knockout significantly ameliorated tubulointerstitial fibrosis in two models of hypoxia-induced CKD. Further, we found that tubular HIF-1α CTAD transcriptionally regulated HK2 and subsequently induced proinflammatory and profibrotic tubule phenotype. Mechanistically, HK2 deficiency, which resulted from HIF-1α CTAD knockout, ameliorated tubulointerstitial fibrosis through inhibiting glycolysis. HK2 overexpression markedly promoted tubulointerstitial fibrosis by inducing proinflammatory and profibrotic tubule phenotype in <em>HIF-1α CTAD</em>^{<em>−/−</em>} mice. Finally, glycolysis inhibition with a specific inhibitor significantly ameliorated tubulointerstitial fibrosis and reduced proinflammatory and profibrotic tubule phenotype in CKD mice.</div></div><div><h3>Conclusions</h3><div>Activation of HIF-1α CTAD promotes hypoxia-induced tubulointerstitial fibrosis through hexokinase 2-mediated glycolysis. Our findings suggested that the HIF-1α CTAD-HK2 pathway represents a novel mechanism of the kidney responses to hypoxia in CKD, providing a promising therapeutic strategy for hypoxia-induced CKD.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111531"},"PeriodicalIF":4.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"tRNA methyltransferase DNMT2 promotes hepatocellular carcinoma progression and enhances Bortezomib resistance through inhibiting TNFSF10","authors":"Junzhong Lai ,&nbsp;Linqin Chen ,&nbsp;Qiumei Li ,&nbsp;Guangjian Zhao ,&nbsp;Xinxin Li ,&nbsp;Dong Guo ,&nbsp;Zhirong Chen ,&nbsp;Yong Zhang ,&nbsp;Jiqiang Fan ,&nbsp;Heng Zhao ,&nbsp;Jiadi Liang ,&nbsp;Ling Tian ,&nbsp;Xiaolan Chen ,&nbsp;Jizhen Lin ,&nbsp;Qi Chen","doi":"10.1016/j.cellsig.2024.111533","DOIUrl":"10.1016/j.cellsig.2024.111533","url":null,"abstract":"<div><div>The tRNA methyltransferase <em>DNMT2</em> (TRDMT1) plays a crucial role in various biological functions; however, its role in cancer, particularly in liver cancer, remains incompletely understood. In this study, we demonstrate that high <em>DNMT2</em> expression is negatively correlated with prognosis in clinical liver cancer patients. A series of <em>in vitro</em> and <em>in vivo</em> experiments showed that <em>DNMT2</em> promotes the proliferation, colony formation, and metastasis of hepatocellular carcinoma cells. We identified the pro-apoptotic gene <em>TNFSF10</em> (TRAIL) as a downstream target of <em>DNMT2</em>, regulated by the N6-methyladenosine (m6A) demethylase <em>FTO</em>. Epigenetically, <em>DNMT2</em> deletion increased <em>FTO</em> expression, leading to a reduction in m6A methylation levels. <em>FTO</em> upregulated <em>TNFSF10</em> expression, significantly reducing the proliferation and metastasis of <em>DNMT2</em>-deficient hepatocellular carcinoma cells. Furthermore, <em>DNMT2</em> deletion was shown to significantly upregulate chemokine expression in tumors. Finally, we demonstrated that the NF-κB inhibitor Bortezomib further enhances <em>DNMT2</em> deletion-induced apoptosis in hepatocellular carcinoma cells. This study reveals <em>DNMT2</em>'s role in liver cancer and presents a new therapeutic target for future treatments.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"127 ","pages":"Article 111533"},"PeriodicalIF":4.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142766624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The mechanism of baicalin in improving pulmonary inflammatory response and injury and regulating intestinal flora in Mycoplasma pneumoniae pneumonia mice","authors":"Dan Song ,&nbsp;Wenfeng Wei ,&nbsp;Jie Zhang ,&nbsp;Lu Zhang ,&nbsp;Jinhai Huo ,&nbsp;Weiming Wang","doi":"10.1016/j.cellsig.2024.111530","DOIUrl":"10.1016/j.cellsig.2024.111530","url":null,"abstract":"<div><h3>Objective</h3><div><em>Mycoplasma pneumoniae</em> (MP) is a common pathogen that can cause respiratory infections. We explored the mechanisms of baicalin (BIA) affecting pulmonary inflammation and injury and regulated their intestinal flora through the TLR4/NF-κB pathway in MP pneumonia (MPP) mice with intestinal dysbiosis.</div></div><div><h3>Methods</h3><div>The intestinal dysbiosis and the MPP mouse models with intestinal dysbiosis were established and treated with different doses of BIA, with lung wet-to-dry weight (W/D) ratio weighed. Kits were conducted to detect MP expression and serum C-reactive protein (CRP)/INF-γ/TNF-α/IL-1β/IL-8 levels, and RT-qPCR and Western blot to determine TLR4/MyD88/NF-κBp65 levels. Lung injury was assessed using HE staining, and intestinal flora structure using 16S rDNA sequencing. Gas chromatography-mass spectrometry determined fecal short-chain fatty acid (SFCA) content.</div></div><div><h3>Results</h3><div>The broad-spectrum antibiotic mixture caused enlarged cecum, increased contents, darker color, weight loss, decreased intestinal flora abundance and diversity, and intestinal flora structure imbalance in mice. The MP-infected intestinal dysbiosis mice exhibited elevated MP expression, reduced body weight, increased W/D ratio, elevated serum CRP/INF-γ/TNFα/IL-1β/IL-8 levels, as well as interstitial pneumonitis in lungs. TLR4/MyD88/NF-κB p65 were elevated in lung tissues of MPP mice with intestinal dysbiosis. BIA partially reversed pulmonary inflammation and injury, and restored the flora diversity and SCFAs in MPP mice with intestinal dysbiosis.</div></div><div><h3>Conclusion</h3><div>BIA attenuated pulmonary inflammation and injury and modulated their intestinal flora imbalance by inhibiting the TLR4/NF-κB pathway in MPP mice with intestinal dysbiosis.</div></div>","PeriodicalId":9902,"journal":{"name":"Cellular signalling","volume":"126 ","pages":"Article 111530"},"PeriodicalIF":4.4,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142738621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}