Journal of respiratory biology and translational medicine最新文献

{"title":"Arrestin beta 1 Regulates Alveolar Progenitor Renewal and Lung Fibrosis.","authors":"Guanling Huang, Yan Geng, Vrishika Kulur, Ningshan Liu, Xue Liu, Forough Taghavifar, Jiurong Liang, Paul W Noble, Dianhua Jiang","doi":"10.35534/jrbtm.2024.10006","DOIUrl":"10.35534/jrbtm.2024.10006","url":null,"abstract":"<p><p>The molecular mechanisms that regulate progressive pulmonary fibrosis remain poorly understood. Type 2 alveolar epithelial cells (AEC2s) function as adult stem cells in the lung. We previously showed that there is a loss of AEC2s and a failure of AEC2 renewal in the lungs of idiopathic pulmonary fibrosis (IPF) patients. We also reported that beta-arrestins are the key regulators of fibroblast invasion, and beta-arrestin 1 and 2 deficient mice exhibit decreased mortality, decreased matrix deposition, and increased lung function in bleomycin-induced lung fibrosis. However, the role of beta-arrestins in AEC2 regeneration is unclear. In this study, we investigated the role and mechanism of Arrestin beta 1 (ARRB1) in AEC2 renewal and in lung fibrosis. We used conventional deletion as well as cell type-specific deletion of <i>ARRB1</i> in mice and found that <i>Arrb1</i> deficiency in fibroblasts protects mice from lung fibrosis, and the knockout mice exhibit enhanced AEC2 regeneration in vivo, suggesting a role of fibroblast-derived ARRB1 in AEC2 renewal. We further found that <i>Arrb1</i>-deficient fibroblasts promotes AEC2 renewal in 3D organoid assays. Mechanistically, we found that CCL7 is among the top downregulated cytokines in <i>Arrb1</i> deficient fibroblasts and CCL7 inhibits AEC2 regeneration in 3D organoid experiments. Therefore, fibroblast ARRB1 mediates AEC2 renewal, possibly by releasing chemokine CCL7, leading to fibrosis in the lung.</p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11087074/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912167","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Solute Carrier Family 26 Member 4 (SLC26A4), A Potential Therapeutic Target for Asthma.","authors":"Vineeta Guntupalli, Rongjun Wan, Liyuan Liu, Wenjing Gu, Shaobing Xie, Peisong Gao","doi":"10.35534/jrbtm.2024.10011","DOIUrl":"10.35534/jrbtm.2024.10011","url":null,"abstract":"<p><p>Asthma is a prevalent respiratory condition with multifaceted pathomechanisms, presenting challenges for therapeutic development. The SLC (Solute Carrier) gene family, encompassing diverse membrane transport proteins, plays pivotal roles in various human diseases by facilitating solute movement across biological membranes. These solutes include ions, sugars, amino acids, neurotransmitters, and drugs. Mutations in these ion channels have been associated with numerous disorders, underscoring the significance of SLC gene families in physiological processes. Among these, the SLC26A4 gene encodes pendrin, an anion exchange protein involved in transmembrane transport of chloride, iodide, and bicarbonate. Mutations in SLC26A4 are associated with Pendred syndrome. Elevated SLC26A4 expression has been linked to airway inflammation, hyperreactivity, and mucus production in asthma. Here, we review novel insights from SLC gene family members into the mechanisms of substrate transport and disease associations, with specific emphasis on SLC26A4. We explore triggers inducing SLC26A4 expression and its contributions to the pathogenesis of pulmonary diseases, particularly asthma. We summarize the inhibitors of SLC26A4 that have shown promise in the treatment of different phenotypes of diseases. While SLC26A4 inhibitors present potential treatments for asthma, further research is imperative to delineate their precise role in asthma pathogenesis and develop efficacious therapeutic strategies targeting this protein.</p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11296660/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141891516","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single Cell Analysis of Lung Lymphatic Endothelial Cells and Lymphatic Responses during Influenza Infection.","authors":"Jian Ge, Hongxia Shao, Hongxu Ding, Yuefeng Huang, Xuebing Wu, Jie Sun, Jianwen Que","doi":"10.35534/jrbtm.2024.10003","DOIUrl":"10.35534/jrbtm.2024.10003","url":null,"abstract":"<p><p>Tissue lymphatic vessels network plays critical roles in immune surveillance and tissue homeostasis in response to pathogen invasion, but how lymphatic system <i>per se</i> is remolded during infection is less understood. Here, we observed that influenza infection induces a significant increase of lymphatic vessel numbers in the lung, accompanied with extensive proliferation of lymphatic endothelial cells (LECs). Single-cell RNA sequencing illustrated the heterogeneity of LECs, identifying a novel PD-L1⁺ subpopulation that is present during viral infection but not at steady state. Specific deletion of <i>Pd-l1</i> in LECs elevated the expansion of lymphatic vessel numbers during viral infection. Together these findings elucidate a dramatic expansion of lung lymphatic network in response to viral infection, and reveal a PD-L1⁺ LEC subpopulation that potentially modulates lymphatic vessel remolding.</p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962217/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Regulation of Transforming Growth Factor-β1-induced Thioredoxin-interacting Protein Ubiquitination and Proteasomal Degradation in Lung Fibroblasts: Implication in Pulmonary Fibrosis.","authors":"Sarah J Taleb, Qinmao Ye, Boina Baoyinna, Michael Dedad, Dakshin Pisini, Narasimham L Parinandi, Lewis C Cantley, Jing Zhao, Yutong Zhao","doi":"10.35534/jrbtm.2024.10002","DOIUrl":"10.35534/jrbtm.2024.10002","url":null,"abstract":"<p><p>Thioredoxin-interacting protein (TXNIP) plays a critical role in regulation of cellular redox reactions and inflammatory responses by interacting with thioredoxin (TRX) or the inflammasome. The role of TXNIP in lung fibrosis and molecular regulation of its stability have not been well studied. Therefore, here we investigated the molecular regulation of TXNIP stability and its role in TGF-β1-mediated signaling in lung fibroblasts. TXNIP protein levels were significantly decreased in lung tissues from bleomycin-challenged mice. Overexpression of TXNIP attenuated transforming growth factor-β1 (TGF-β1)-induced phosphorylation of Smad2/3 and fibronectin expression in lung fibroblasts, suggesting that decrease in TXNIP may contribute to the pathogenesis of lung fibrosis. Further, we observed that TGF-β1 lowered TXNIP protein levels, while <i>TXNIP</i> mRNA levels were unaltered by TGF-β1 exposure. TGF-β1 induced TXNIP degradation via the ubiquitin-proteasome system. A serine residue mutant (TNXIP-S308A) was resistant to TGF-β1-induced degradation. Furthermore, downregulationof ubiquitin-specific protease-13 (USP13) promoted the TGF-β1-induced TXNIP ubiquitination and degradation. Mechanistic studies revealed that USP13 targeted and deubiquitinated TXNIP. The results of this study revealed that the decrease of TXNIP in lungs apparently contributes to the pathogenesis of pulmonary fibrosis and that USP13 can target TXNP for deubiquitination and regulate its stability.</p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10962057/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140290145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Asthma Risk Gene, <i>GSDMB</i>, Promotes Mitochondrial DNA-induced <i>ISGs</i> Expression.","authors":"Tao Liu, Julian Hecker, Siqi Liu, Xianliang Rui, Nathan Boyer, Jennifer Wang, Yuzhen Yu, Yihan Zhang, Hongmei Mou, Luis Guillermo Gomez-Escobar, Augustine M K Choi, Benjamin A Raby, Scott T Weiss, Xiaobo Zhou","doi":"10.35534/jrbtm.2024.10005","DOIUrl":"10.35534/jrbtm.2024.10005","url":null,"abstract":"<p><p>Released mitochondrial DNA (mtDNA) in cells activates cGAS-STING pathway, which induces expression of interferon-stimulated genes (ISGs) and thereby promotes inflammation, as frequently seen in asthmatic airways. However, whether the genetic determinant, Gasdermin B (GSDMB), the most replicated asthma risk gene, regulates this pathway remains unknown. We set out to determine whether and how GSDMB regulates mtDNA-activated cGAS-STING pathway and subsequent <i>ISGs</i> induction in human airway epithelial cells. Using qPCR, ELISA, native polyacrylamide gel electrophoresis, co-immunoprecipitation and immunofluorescence assays, we evaluated the regulation of GSDMB on cGAS-STING pathway in both BEAS-2B cells and primary normal human bronchial epithelial cells (nHBEs). mtDNA was extracted in plasma samples from human asthmatics and the correlation between mtDNA levels and eosinophil counts was analyzed. <i>GSDMB</i> is significantly associated with <i>RANTES</i> expression in asthmatic nasal epithelial brushing samples from the Genes-environments and Admixture in Latino Americans (GALA) II study. Over-expression of <i>GSDMB</i> promotes DNA-induced IFN and <i>ISGs expression</i> in bronchial epithelial BEAS-2B cells and nHBEs. Conversely, knockout of <i>GSDMB</i> led to weakened induction of <i>interferon</i> (IFNs) and <i>ISGs</i> in BEAS-2B cells. Mechanistically, GSDMB interacts with the C-terminus of STING, promoting the translocation of STING to Golgi, leading to the phosphorylation of IRF3 and induction of <i>IFNs</i> and <i>ISGs</i>. mtDNA copy number in serum from asthmatics was significantly correlated with blood eosinophil counts especially in male subjects. GSDMB promotes the activation of mtDNA and poly (dA:dT)-induced activation of cGAS-STING pathway in airway epithelial cells, leading to enhanced induction of <i>ISGs.</i></p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11086750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Progress and Gaps in Respiratory Disease Research and Treatment: Highlights of the IRM 2024 in Shanghai.","authors":"Jin-San Zhang, Qhaweni Dhlamini, Qiang Guo, Meiyu Quan, Jin Wu, Handeng Lyu, Lei Chong, Yuqing Lv, Yuting Lin, Bin Zhou, Yuru Liu, Honglong Ji, Xinhua Lin, Wen Ning, Pengfei Sui, Huaiyong Chen, Peisong Gao, Wei Chen, Xiaobo Zhou, Yuanlin Song, Chaoqun Wang, Xiao Su, Jinfu Xu, Jie Sun, Yin Chen, Yan Geng, Hai Song, Hongbin Ji, Yuanpu Peter Di, Hao Tang, Chao Lu, Jinghong Li, Ke Cheng, Mengshu Cao, Jiurong Liang, Yingze Zhang, Yang Zhou, Ying Xi, Weining Xiong, Bin Cao, Jianwen Que, Dianhua Jiang","doi":"10.70322/jrbtm.2024.10021","DOIUrl":"10.70322/jrbtm.2024.10021","url":null,"abstract":"<p><p>Respiratory diseases pose a major public health challenge globally, necessitating collaborative efforts between basic researchers and clinicians for effective solutions. China, which is heavily impacted by a broad spectrum of respiratory disorders, has made notable strides in both research and clinical management of these diseases. The International Respiratory Medicine (IRM) meeting was organized with the primary goal of facilitating the exchange of recent research developments and promoting collaboration between Chinese and American scientists in both basic and clinical research fields. This article summarizes key insights from IRM2024, held in Shanghai, where a wide range of topics were discussed, including lung tissue development, disease mechanisms, and innovative therapeutic strategies. By integrating perspectives from basic, translational, and clinical research, IRM2024 highlighted recent advancements, addressed persistent challenges, and explored future directions in respiratory science and clinical practice. The insights gained from IRM2024 are poised to be pivotal in shaping future research and therapeutic approaches, further reinforcing the global commitment to enhancing respiratory health and improving patient outcomes.</p>","PeriodicalId":517993,"journal":{"name":"Journal of respiratory biology and translational medicine","volume":"1 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11661833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}