Your browser doesn't support javascript.
loading
Spatially Resolved Identification of Transglutaminase Substrates by Proteomics in Pulmonary Fibrosis.
Takeuchi, Taishu; Tatsukawa, Hideki; Shinoda, Yoshiki; Kuwata, Keiko; Nishiga, Miyuki; Takahashi, Hiroshi; Hase, Naoki; Hitomi, Kiyotaka.
Affiliation
  • Takeuchi T; Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, and.
  • Tatsukawa H; Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, and.
  • Shinoda Y; Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, and.
  • Kuwata K; Institute of Transformative Bio-Molecules, Nagoya University, Tokai National Higher Education and Research System, Furo-cho, Chikusa, Nagoya, Japan; and.
  • Nishiga M; Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Takahashi H; Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Hase N; Teijin Institute for Bio-Medical Research, Teijin Pharma Limited, Hino, Tokyo, Japan.
  • Hitomi K; Cellular Biochemistry Laboratory, Graduate School of Pharmaceutical Sciences, and.
Am J Respir Cell Mol Biol ; 65(3): 319-330, 2021 09.
Article in En | MEDLINE | ID: mdl-34264172
Idiopathic pulmonary fibrosis (IPF) is characterized by the invariably progressive deposition of fibrotic tissue in the lungs and overall poor prognosis. TG2 (transglutaminase 2) is an enzyme that crosslinks glutamine and lysine residues and is involved in IPF pathogenesis. Despite the accumulating evidence implicating TG2 as a critical enzyme, the causative function and direct target of TG2 relating to this pathogenesis remain unelucidated. Here, we clarified the distributions of TG2 protein/activity and conducted quantitative proteomics analyses of possible substrates crosslinked by TG2 on unfixed lung sections in a mouse pulmonary fibrosis model. We identified 126 possible substrates as markedly TG2-dependently increased in fibrotic lung. Gene ontology analysis revealed that these identified proteins were mostly enriched in the lipid metabolic process, immune system process, and protein transport. In addition, these proteins were enriched in 21 pathways, including phagosome, lipid metabolism, several immune responses, and protein processing in endoplasmic reticulum. Furthermore, the network analyses screened out the six clusters and top 20 hub proteins with higher scores, which are related to endoplasmic reticulum stress and peroxisome proliferator-activated receptor signals. Several enriched pathways and categories were identified, some of which were the same terms based on transcription analysis in IPF. Our results provide novel pathological molecular networks driven by protein crosslinking via TG2, which can lead to the development of new therapeutic targets for IPF.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Signal Transduction / Transglutaminases / GTP-Binding Proteins / Proteomics / Lung Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals Language: En Journal: Am J Respir Cell Mol Biol Journal subject: BIOLOGIA MOLECULAR Year: 2021 Document type: Article Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Pulmonary Fibrosis / Signal Transduction / Transglutaminases / GTP-Binding Proteins / Proteomics / Lung Type of study: Diagnostic_studies / Prognostic_studies Limits: Animals Language: En Journal: Am J Respir Cell Mol Biol Journal subject: BIOLOGIA MOLECULAR Year: 2021 Document type: Article Country of publication: United States