Study of the metallo-peptidase PHEX involvement in physiological and pathophysiological processes

• Grant number: 11/50495-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2011
• End date: December 31, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Nilana Meza Tenório de Barros Jaggi
• Grantee: Nilana Meza Tenório de Barros Jaggi
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The PHEX gene (phosphate-regulating gene with homologies to endopeptidase on the X chromosome) was initialIy identified as the gene mutated in patients with a prevalent form (1:20,000) of human hereditary rickets called X-Linked Hypophosphatemia (X -linked hypophosphataemia - XLH) and resuIts in a membrane metallopeptidase with high homology to the eprilysin (NEP). The XLH is characterized by defects in the phosphate reabsorption and vitamin D metabolism and the patients with this disorder typically exhibit growth retardation, rickets, dental abscess, osteomalacia and defects in bone mineralization. However, it still remains unknown how the PHEX / PHEX (gene / protein) can generate the clinical and biochemical characteristics in patients with XLH and in "Hyp mo use". The aim of this project is to advance in characterization and knowledge of physiological function of PHEX. Based in some preliminary data from our laboratory, we will foeus on identifying its natural substrates, investigating their possible involvement in tumor proliferation and the involvement of PHEX in differentiation process of osteoblasts. We also propose an effective biochemical characterization, the development of selective substrates and inhibitors for PHEX. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OLIVEIRA, MARCELA; ASSIS, DIEGO M.; PASCHOALIN, THAYSA; MIRANDA, ANTONIO; RIBEIRO, ELIANE B.; JULIANO, MARIA A.; BROEMME, DIETER; CHRISTOFFOLETE, MARCELO AUGUSTO; BARROS, NILANA M. T.; CARMONA, ADRIANA K.. Cysteine cathepsin S processes leptin, inactivating its biological activity. Journal of Endocrinology, v. 214, n. 2, p. 217-224, AUG 2012. (11/50495-0, 08/10700-1)

BARROS, NILANA M. T.; HOAC, BETTY; NEVES, RAQUEL L.; ADDISON, WILLIAM N.; ASSIS, DIEGO M.; MURSHED, MONZUR; CARMONA, ADRIANA K.; MCKEE, MARC D.. Proteolytic processing of osteopontin by PHEX and accumulation of osteopontin fragments in Hyp mouse bone, the murine model of X-linked hypophosphatemia. Journal of Bone and Mineral Research, v. 28, n. 3, p. 688-699, MAR 2013. (11/50495-0)