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

Details

• Personal Author:
  Hettick JM ; Law, Brandon F. ; Lin C-C ; Hettick JM ; Law, Brandon F. ; Lin C-C
• Description:
  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. [Description provided by NIOSH]
• Subjects:
  Asthma, Occupational Blood Isocyanates Macrophages Occupational Health Safety
• Keywords:
  4,4-Methylene Diphenyl Diisocyanate Author Keywords: 4,4'-methylene Diphenyl Diisocyanate Cell Signaling CircRNAs Circular RNAs Gene Expression Hsa-miR-206-3p KLF4 Krüppel-like Factor 4 MDI OA Occupational Asthma

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• ISSN:
  2073-4409
• Document Type:
  Text
• Genre:
  Journal Article ; Journal Article
• Place as Subject:
  Philadelphia Region [OSHA] ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH) ; National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health ; Workplace Safety & Health
• Location:
  North America ; North America
• Volume:
  13
• Issue:
  20
• NIOSHTIC Number:
  nn:20070232
• Citation:
  Cells 2024 Oct; 13(20):1725
• Contact Point Address:
  Chen-Chung Lin, Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA
• Email:
  mjy2@cdc.gov
• CAS Registry Number:
  Diphenylmethane diisocyanate (CAS RN 101-68-8) ; Diphenylmethane diisocyanate (CAS RN 101-68-8)
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Manufacturing ; Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Cells
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:e3e68bbf5471fc8e51f173cd042ba24f75edf69e12d20ace279eb4df4a8edf7205927adb44a6b9451843fd15e35d62ab5bb6c325595722d1eac4893050e8b433
• Download URL:
  https://stacks.cdc.gov/view/cdc/208482/cdc_208482_DS1.pdf
• File Type:
  [PDF - 5.44 MB ]