Expression of optineurin isolated from rat-injured dental pulp and the effects on inflammatory signals in normal rat kidney cells

• Published in: Odontology Vol. 106; no. 2; pp. 135 - 144
• Main Authors: Senoo, Kyoko, Yamashiro, Keisuke, Yamamoto, Tadashi, Myokai, Fumio, Kawamura, Mari, Takashiba, Shogo
• Format: Journal Article
• Language: English
• Published: Tokyo The Society of the Nippon Dental University 01.04.2018; Springer Japan; Springer Nature B.V
• Subjects: Animals; Apoptosis; Blotting, Western; c-Jun protein; Cell growth; Cell Proliferation; Cells, Cultured; Cytokines - metabolism; Cytoplasm; Dental pulp; Dental Pulp - cytology; Dental Pulp - drug effects; Dental Pulp - metabolism; Dentistry; Enzyme-Linked Immunosorbent Assay; Fibroblasts; Hydrogen peroxide; Hydrogen Peroxide - pharmacology; Immunohistochemistry; Inflammation; Intracellular; Intracellular Signaling Peptides and Proteins - metabolism; Intracellular signalling; JNK protein; Kidney - cytology; Kinases; Localization; Medicine; Microarray Analysis; Monocyte chemoattractant protein 1; Nuclei; Oral and Maxillofacial Surgery; Original Article; Phagocytosis; Proteins; Rats; Reverse Transcriptase Polymerase Chain Reaction; Rodents; Signal Transduction; siRNA; Transcription Factor TFIIIA - metabolism; Transcription factors; Transfection; Tumor Necrosis Factor-alpha - pharmacology; Tumor necrosis factor-TNF; Tumor necrosis factor-α; Inflammation; Optineurin; FIP-2; Apoptosis; Dental pulp
• ISSN: 1618-1247; 1618-1255
• DOI: 10.1007/s10266-017-0314-5

[Abstract] We previously isolated rat 14.7K-interacting protein-2 (rFIP-2) from the rat-wounded pulp. The protein, homologous to human FIP-2, is known as optineurin and was initially identified as a novel tumor necrosis factor-α (TNFα)-inducible protein, and more recently, as an autophagy receptor. However, the biological role of optineurin in dental pulp remains elusive. We hypothesized that optineurin has a crucial role in regulating molecular processes during pulp inflammatory responses induced by TNF-α. We examined the kinetics of optineurin expression in pulp inflammation. Optineurin localization and expression were examined using rat pulp fibroblasts. The cells were treated with pharmacological inhibitors for TNF-α-induced inflammatory signals or with hydrogen peroxide as apoptotic stimuli. Stable optineurin-knockdown cells (OPTN-KD cells) were established by transfecting normal rat kidney cells with a vector expressing optineurin-specific small interfering RNA. Cell proliferation and the profiles of cytokines and intracellular signaling molecules were examined using OPTN-KD cells stimulated by TNF-α. Optineurin was localized in the cytoplasm and then translocated into the nucleus upon apoptotic stimuli. Optineurin expression was increased by TNF-α and decreased by a specific inhibitor of c-Jun N-terminal kinase. The OPTN-KD cells secreted smaller amounts of monocyte chemotactic protein-1 (MCP-1) and intracellular MCP-1 mRNA, and cell proliferation was significantly increased. Apoptosis-related signaling molecules were down-regulated in OPTN-KD cells. These results demonstrated that optineurin is a crucial molecule mediated by TNF-α, which induces the production of inflammatory factors and apoptosis signaling, suggesting the presence of signaling interactions between optineurin and a transcription factor for MCP-1.