Salt-inducible kinases: new players in pulmonary arterial hypertension?

Autores da FMUP

• Patrício Manuel Vieira Araújo Soares Da Silva

  Autor

• António Pedro De Barros Gomes

  Autor

Participantes de fora da FMUP

• Antonio, Tatiana
• Pires, Nuno M.

Unidades de investigação

• Biomedicina

Abstract

Salt-inducible kinases (SIKs) are serine/threonine kinases belonging to the AMP -activated protein kinase (AMPK) family. Accumulating evidence indicates that SIKs phosphorylate multiple targets, including histone deacetylases (HDACs) and cAMP response element-binding protein (CREB)-regulated transcriptional coactivators (CRTCs), to coordinate signaling pathways implicated in metabolism, cell growth, proliferation, apoptosis, and inflammation. These pathways down-stream of SIKs are altered not only in pathologies like cancer, systemic hyperten-sion, and inflammatory diseases, but also in pulmonary arterial hypertension (PAH), a multifactorial disease characterized by pulmonary vasoconstriction, inflammation and remodeling of pulmonary arteries owing to endothelial dysfunc-tion and aberrant proliferation of smooth muscle cells (SMCs). In this opinion arti-cle, we present evidence of SIKs as modulators of key signaling pathways involved in PAH pathophysiology and discuss the potential of SIKs as therapeutic targets for PAH, emphasizing the need for deeper molecular insights on PAH.

Copyright © 2022 Elsevier Ltd. All rights reserved.

Keywords

• SMOOTH-MUSCLE-CELLS; NA+,K+-ATPASE ACTIVITY; PROTEIN-KINASE; INHIBITION; TRANSCRIPTION; NETWORK; SIK2