Science and Research

Ltbp4 regulates Pdgfrbeta expression via TGFbeta-dependent modulation of Nrf2 transcription factor function

Latent transforming growth factor beta binding protein 4 (LTBP4) belongs to the fibrillin/LTBP family of proteins and plays an important role as a structural component of extracellular matrix (ECM) and local regulator of TGFbeta signaling. We have previously reported that Ltbp4S knock out mice (Ltbp4S-/-) develop centrilobular emphysema reminiscent of late stage COPD, which could be partially rescued by inactivating the antioxidant protein Sestrin 2 (Sesn2). More recent studies showed that Sesn2 knock out mice upregulate Pdgfrbeta-controlled alveolar maintenance programs that protect against cigarette smoke induced pulmonary emphysema. Based on this, we hypothesized that the emphysema of Ltbp4S-/- mice is primarily caused by defective Pdgfrbeta signaling. Here we show that LTBP4 induces Pdgfrbeta signaling by inhibiting the antioxidant Nrf2/Keap1 pathway in a TGFbeta-dependent manner. Overall, our data identified Ltbp4 as a major player in lung remodeling and injury repair.

  • Tomasovic, A.; Kurrle, N.; Wempe, F.; De-Zolt, S.; Scheibe, S.; Koli, K.; Serchinger, M.; Schnutgen, F.; Surun, D.; Sterner-Kock, A.; Weissmann, N.; von Melchner, H.

Keywords

  • Copd
  • Emphysema
  • Ltbp4
  • Nrf2
  • Pdgfrbeta
  • Ros
  • Tgfbeta
Publication details
DOI: 10.1016/j.matbio.2016.09.006
Journal: Matrix biology : journal of the International Society for Matrix Biology
Pages: 109-120 
Work Type: Original
Location: UGMLC
Disease Area: COPD
Partner / Member: JLU
Access-Number: 27645114
See publication on PubMed

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