Identification of the α isoform of preprotachykinin-A mRNA in synovial fibroblasts isolated from patients with rheumatoid arthritis

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概要

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• Previous study showed that synovial fibroblasts derived from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) express β-preprotachykinin (PPT)-A mRNA and release substance P (SP). In this study, we examined the presence of an isoform of PPT-A mRNA in synovial and normal skin fibroblasts by reverse transcription-polymerase chain reaction (RT-PCR) analysis. RA synovial fibroblasts, but not OA synovial and skin fibroblasts, expressed α-isoform PPT-A mRNA together with β-PPT-A mRNA. However, expression of γ- and δ-PPT mRNAs was not observed in synovial and skin fibroblasts. Levels of both α- and β-PPT-A mRNAs were increased in RA fibroblasts treated with transforming growth factor (TGF)-β and basic fibroblast growth factor (bFGF). Treatment with TGF-β and bFGF strongly increased the expression of α- and β-PPT-A mRNAs compared to the individual treatment. Peak levels of α-PPT-A mRNA were reached at 8h whereas those of β-PPT-A mRNA were maximal at 12h after treatment with TGF-β and bFGF. These findings suggest that SP production by synovial fibroblasts in RA is regulated through signaling pathways that lead to the generation of both α- and β-PPT-A mRNAs.

• 日本学士院の論文

著者

• Abe Kazuki

  Pharmacological Research Department Research Laboratory Minophagen Pharmaceutical Co. Ltd.

• SATO Toshitsugu

  Research Laboratory, Minophagen Pharmaceutical Co., Ltd.

• NISHIKAWA Takuji

  Department of Orthopaedic Surgery, University of Tokyo

• Koshihara Yasuko

  Department Of Biosignal Research Tokeyo Metropolitan Institute Of Gerontology

• Inoue Hideo

  Research Laboratory Minophagen Pharmaceutical Co.

• ABE Kazuki

  Research Laboratory, Minophagen Pharmaceutical Co.

• YAMAMOTO Seizou

  Department of Orthopedic Surgery, Tokyo Metropolitan Geriatric Medical Hospital

• HIRABAYASHI Kazuhiro

  Research Laboratory, Minophagen Pharmaceutical Co.

• Nishikawa Takuji

  Department Of Orthopaedic Surgery University Of Tokyo

• KOSHIHARA Yasuko

  Department of Nutrition, Tokyo Metropolitan Institute of Gerontology

• NISHIKAWA Takuji

  Department of Orthopedic Surgery, University of Tokyo

• INOUE Hideo

  Research Laboratory, Minophagen Pharmaceutical Co.

• SATO Toshitsugu

  Research Laboratory, Minophagen Pharmaceutical Co.

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