{"title":"环状 RNA hsa_circ_0008726 靶向 hsa-miR-206-3p/KLF4 轴,调节巨噬细胞中 4,4'-亚甲基二苯基二异氰酸酯-谷胱甘肽共轭物诱导的趋化因子转录。","authors":"Chen-Chung Lin, Brandon F Law, Justin M Hettick","doi":"10.3390/cells13201725","DOIUrl":null,"url":null,"abstract":"<p><p>Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (<i>hsa/mmu</i>)-microRNA<i>(miR)-206-3p</i>, resulting in the activation of <i>mmu/hsa-miR-206-3p</i>-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate <i>hsa-miR-206-3p</i>. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate <i>hsa-miR-206-3p</i> in macrophages. The expression of candidate <i>hsa-miR-206-3p</i>-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced <i>hsa_circ_0008726</i> and its host gene transcript <i>DNAJB6</i>, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that <i>hsa-miR-206-3p</i> can bind to <i>hsa_circ_0008726</i>. The expressions of endogenous <i>hsa-miR-206-3p</i>, <i>hsa-miR-206-3p</i>-regulated <i>KLF4</i>, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of <i>hsa_circ_0008726</i> siRNAs or <i>hsa_circ_0008726</i> overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i> via induction of endogenous <i>hsa_circ_0008726/DNAJB6</i>, resulting in the upregulation of <i>hsa-miR-206-3p</i>-mediated regulations in macrophages.</p>","PeriodicalId":9743,"journal":{"name":"Cells","volume":null,"pages":null},"PeriodicalIF":5.1000,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505732/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circular RNA <i>hsa_circ_0008726</i> Targets the <i>hsa-miR-206-3p</i>/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.\",\"authors\":\"Chen-Chung Lin, Brandon F Law, Justin M Hettick\",\"doi\":\"10.3390/cells13201725\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (<i>hsa/mmu</i>)-microRNA<i>(miR)-206-3p</i>, resulting in the activation of <i>mmu/hsa-miR-206-3p</i>-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate <i>hsa-miR-206-3p</i>. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate <i>hsa-miR-206-3p</i> in macrophages. The expression of candidate <i>hsa-miR-206-3p</i>-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced <i>hsa_circ_0008726</i> and its host gene transcript <i>DNAJB6</i>, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that <i>hsa-miR-206-3p</i> can bind to <i>hsa_circ_0008726</i>. The expressions of endogenous <i>hsa-miR-206-3p</i>, <i>hsa-miR-206-3p</i>-regulated <i>KLF4</i>, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of <i>hsa_circ_0008726</i> siRNAs or <i>hsa_circ_0008726</i> overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates <i>hsa-miR-206-3p</i> via induction of endogenous <i>hsa_circ_0008726/DNAJB6</i>, resulting in the upregulation of <i>hsa-miR-206-3p</i>-mediated regulations in macrophages.</p>\",\"PeriodicalId\":9743,\"journal\":{\"name\":\"Cells\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":5.1000,\"publicationDate\":\"2024-10-18\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11505732/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cells\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/cells13201725\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cells","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/cells13201725","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Circular RNA hsa_circ_0008726 Targets the hsa-miR-206-3p/KLF4 Axis to Modulate 4,4'-Methylene Diphenyl Diisocyanate-Glutathione Conjugate-Induced Chemokine Transcription in Macrophages.
Exposure to 4,4'-methylene diphenyl diisocyanate (MDI) in the workplace may lead to the development of occupational asthma (OA). However, the specific mechanism(s) by which MDI induces OA are poorly understood. Previous reports have demonstrated that MDI and MDI-glutathione (GSH) conjugate exposure downregulates endogenous human/murine (hsa/mmu)-microRNA(miR)-206-3p, resulting in the activation of mmu/hsa-miR-206-3p-regulated signaling pathways in macrophages. Circular RNAs (circRNAs) regulate many important biological processes by targeting endogenous miRs; however, whether MDI/MDI-GSH exposure may influence circRNA expressions is unknown. Several circRNAs have been identified that regulate hsa-miR-206-3p. We hypothesize that MDI-GSH conjugate exposure induces endogenous circRNA(s) to regulate hsa-miR-206-3p in macrophages. The expression of candidate hsa-miR-206-3p-binding circRNAs was determined from MDI-GSH conjugate-treated differentiated THP-1 macrophages using RT-qPCR. MDI-GSH exposures induced hsa_circ_0008726 and its host gene transcript DNAJB6, whereas other circRNA(s) examined were either not detected or unchanged. RNA-induced silencing complex-immunoprecipitation (RISC-IP) experiments confirm that hsa-miR-206-3p can bind to hsa_circ_0008726. The expressions of endogenous hsa-miR-206-3p, hsa-miR-206-3p-regulated KLF4, and KLF4-activated M2 macrophage-associated markers and chemokines were up-/down-regulated by transfection of hsa_circ_0008726 siRNAs or hsa_circ_0008726 overexpression plasmid in macrophages, respectively. These results suggest MDI-GSH exposure downregulates hsa-miR-206-3p via induction of endogenous hsa_circ_0008726/DNAJB6, resulting in the upregulation of hsa-miR-206-3p-mediated regulations in macrophages.
CellsBiochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
9.90
自引率
5.00%
发文量
3472
审稿时长
16 days
期刊介绍:
Cells (ISSN 2073-4409) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to cell biology, molecular biology and biophysics. It publishes reviews, research articles, communications and technical notes. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. Full experimental and/or methodical details must be provided.