Molecular basis of the association between transcription regulators nuclear respiratory factor 1 and inhibitor of DNA binding protein 3 and the development of microvascular lesions

Microvasc Res. 2022 May:141:104337. doi: 10.1016/j.mvr.2022.104337. Epub 2022 Feb 7.

Abstract

The prognosis of patients with microvascular lesions remains poor because vascular remodeling eventually obliterates the lumen. Here we have focused our efforts on vessel dysfunction in two different organs, the lung and brain. Despite tremendous progress in understanding the importance of blood vessel integrity, gaps remain in our knowledge of the underlying molecular factors contributing to vessel injury, including microvascular lesions. Most of the ongoing research on these lesions have focused on oxidative stress but have not found major molecular targets for the discovery of new treatment or early diagnosis. Herein, we have focused on elucidating the molecular mechanism(s) based on two new emerging molecules NRF1 and ID3, and how they may contribute to microvascular lesions in the lung and brain. Redox sensitive transcriptional activation of target genes depends on not only NRF1, but the recruitment of co-activators such as ID3 to the target gene promoter. Our review highlights the fact that targeting NRF1 and ID3 could be a promising therapeutic approach as they are major players in influencing cell growth, cell repair, senescence, and apoptotic cell death which contribute to vascular lesions. Knowledge about the molecular biology of these processes will be relevant for future therapeutic approaches to not only PAH but cerebral angiopathy and other vascular disorders. Therapies targeting transcription regulators NRF1 or ID3 have the potential for vascular disease-modification because they will address the root causes such as genomic instability and epigenetic changes in vascular lesions. We hope that our findings will serve as a stimulus for further research towards an effective treatment of microvascular lesions.

Keywords: Inhibitor of DNA binding protein 3; Microvascular lesions; Nuclear respiratory factor-1; Redox signaling; Vasculopathy.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Cell Cycle
  • Cell Proliferation
  • DNA-Binding Proteins* / genetics
  • Humans
  • Nuclear Respiratory Factor 1* / genetics
  • Nuclear Respiratory Factor 1* / metabolism
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • Nuclear Respiratory Factor 1
  • Transcription Factors