title: Mycobacterium leprae downregulates the expression of PHEX in Schwann cells and osteoblasts.
abstract: Neuropathy and bone deformities, lifelong sequelae of leprosy that persist after treatment, result in significant impairment to patients and compromise their social rehabilitation. Phosphate-regulating gene with homologies to endopeptidase on the X chromosome (PHEX) is a Zn-metalloendopeptidase, which is abundantly expressed in osteoblasts and many other cell types, such as Schwann cells, and has been implicated in phosphate metabolism and X-linked rickets. Here, we demonstrate that Mycobacterium leprae stimulation downregulates PHEX transcription and protein expression in a human schwannoma cell line (ST88-14) and human osteoblast lineage. Modulation of PHEX expression was observed to a lesser extent in cells stimulated with other species of mycobacteria, but was not observed in cultures treated with latex beads or with the facultative intracellular bacterium Salmonella typhimurium. Direct downregulation of PHEX by M. leprae could be involved in the bone resorption observed in leprosy patients. This is the first report to describe PHEX modulation by an infectious agent.
authors.affiliation: Laboratório de Imunopatologia, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brasil.
authors.forename: Sandra R Boiça
authors.initials: SR
authors.lastname: Silva
authors.forename: Antônio J
authors.initials: AJ
authors.lastname: Tempone
authors.forename: Tatiana P
authors.initials: TP
authors.lastname: Silva
authors.forename: Maria Renata S N
authors.initials: MR
authors.lastname: Costa
authors.forename: Geraldo M B
authors.initials: GM
authors.lastname: Pereira
authors.forename: Flávio A
authors.initials: FA
authors.lastname: Lara
authors.forename: Maria Cristina V
authors.initials: MC
authors.lastname: Pessolani
authors.forename: Danuza
authors.initials: D
authors.lastname: Esquenazi
mesh_terms: D015536:Down-Regulation / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D007918:Leprosy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009166:Mycobacterium leprae; D010006:Osteoblasts / Q000201:enzymology*; D053402:PHEX Phosphate Regulating Neutral Endopeptidase / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012583:Schwann Cells / Q000201:enzymology*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D053402:PHEX Phosphate Regulating Neutral Endopeptidase