Ivonne Loeffler1, Gunter Wolf. 1. Department of Internal Medicine III, University Hospital Jena, Jena, Germany.
Abstract
BACKGROUND: Renal hypoxia is known to play an important role in the pathophysiology of acute renal injury as well as in chronic kidney diseases. The mediators of hypoxia are the transcription factors HIF (hypoxia-inducible factors), that are highly regulated. Under normoxic conditions constitutively expressed HIF-α subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2, and PHD3) and subsequently degraded by proteasomes. MATERIALS AND METHODS: This narrative review is based on the material searched for and obtained via PubMed and MEDLINE up to January 2015. RESULTS: The MAPK organizer 1 (Morg1) has been identified to act as a scaffold protein of PHD3 and suppression of Morg1 leads to the stabilization of HIF-α, which forms in the absence of oxygen a heterodimer with HIF-β, translocates to the nucleus and promotes the transcription of HIF target genes. CONCLUSIONS: This review summarizes the current knowledge regarding the role of hypoxia, HIF signalling, and Morg1 in acute and chronic renal injury.
BACKGROUND:Renal hypoxia is known to play an important role in the pathophysiology of acute renal injury as well as in chronic kidney diseases. The mediators of hypoxia are the transcription factors HIF (hypoxia-inducible factors), that are highly regulated. Under normoxic conditions constitutively expressed HIF-α subunits are hydroxylated by prolyl hydroxylases (PHD1, PHD2, and PHD3) and subsequently degraded by proteasomes. MATERIALS AND METHODS: This narrative review is based on the material searched for and obtained via PubMed and MEDLINE up to January 2015. RESULTS: The MAPK organizer 1 (Morg1) has been identified to act as a scaffold protein of PHD3 and suppression of Morg1 leads to the stabilization of HIF-α, which forms in the absence of oxygen a heterodimer with HIF-β, translocates to the nucleus and promotes the transcription of HIF target genes. CONCLUSIONS: This review summarizes the current knowledge regarding the role of hypoxia, HIF signalling, and Morg1 in acute and chronic renal injury.
Authors: Elisa Conde; Sara Giménez-Moyano; Laura Martín-Gómez; Macarena Rodríguez; M Edurne Ramos; Elia Aguado-Fraile; Ignacio Blanco-Sanchez; Ana Saiz; María Laura García-Bermejo Journal: Sci Rep Date: 2017-01-20 Impact factor: 4.379