Disentangling the spatiotemporal tissue response to inflammation caused by a physical stressor

Details

• Personal Author:
  Boyd JW ; Currie HN ; Han AA ; Miller JV ; Mouch JA ; Prediger MS ; Prince N ; Scardoni G
• Description:
  Investigations of molecular and signaling responses involved in physical injuries have contributed greatly to the advancement of our knowledge regarding inflammation. Intra- and extracellular regulators, such as cytokines, signaling proteins, and growth factors, possess significant roles in facilitating recovery from physical injury. This study explored 30 spatiotemporal responses comprised of cytokines (IL-1alpha, IL-1beta, IL-2, IL-6, TNF-alpha, and MIP-1alpha), proteins (Akt, c-Jun, CREB, ERK1/2, JNK, MEK1, p38, p53, and p90RSK), phosphorylated proteins (p-Akt, p-c-Jun, p-CREB, p-ERK1/2, p-GSK-3 alpha/beta, p-HSP27, p-IkappaBalpha, p-JNK, p-MEK1, p-p38, p-p70S6K, p-p90RSK, p-STAT2, and p-STAT3), and Caspase-3, measured in rat skeletal muscle tissue following a traumatic fracture injury. The dataset was examined using network centrality parameter analysis to assess the impact of each protein response in relation to all other co-measured molecular and signaling responses. The results from the network analysis allowed us to determine the progression of tissue response (from inflammation through new tissue formation), while also identifying the proteins that appear to be regulatory within this complicated framework. Notably, severely damaged tissue showed cellular indications of inflammation and new tissue formation by 168 h post-injury, while tissue 1-cm away from the site of injury (that experienced minor injury) exhibited signs of new tissue formation as early as 24 h post-injury. Extracellular hallmarks of inflammation, cytokines IL-1beta, IL-6, and IL-2 appear to have a pronounced impact at earlier time points (0-24 h post-injury), while intracellular proteins involved in cell proliferation, differentiation, or proteolysis (c-Jun, CREB, JNK, p38, p-c-Jun; p-MEK1, p-p38, p-STAT3) are more significant at later times (24-168 h). Overall, this study offers a prospective spatiotemporal depiction of the intra- and extracellular signaling involved in tissue response to inflammation, and additionally demonstrates the advantages of using a network analysis approach to extract significant information from a complex, multifaceted dataset. [Description provided by NIOSH]
• Subjects:
  Growth Immune System Laboratories Musculoskeletal System Occupational Health Safety Toxicology
• Keywords:
  Analytical Processes Cell Differentiation Cell Proliferation Cell Signaling Cellular Effects Cellular Reactions Cytokines Growth Factors Immune Reaction Immune System Injuries Laboratory Animals Molecular Signaling Muscle Tissue Physiological Response Physiological Stress Proteins Signaling Pathways Skeletal System Tissue Culture

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• ISSN:
  1096-6080
• Document Type:
  Text
• Genre:
  Abstract or Summary
• Place as Subject:
  Maryland ; OSHA Region 3 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  156
• Issue:
  1
• NIOSHTIC Number:
  nn:20049489
• Citation:
  Toxicologist 2017 Mar; 156(1):470
• Federal Fiscal Year:
  2017
• Peer Reviewed:
  False
• Source Full Name:
  The Toxicologist. Society of Toxicology 56th Annual Meeting and ToxExpo, March 12-16, 2017, Baltimore, Maryland
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:86abf5fadac7f01e6ceb4afa7875955d0f772115abf86c2a0348480225ef008e27a9a956df5b6b4f27ec8278365bef29f9a15d1ee8eb336d339338c1fe5a4c7d
• Download URL:
  https://stacks.cdc.gov/view/cdc/203930/cdc_203930_DS1.pdf
• File Type:
  [PDF - 944.42 KB ]