title: Occurrence of minimal change nephrotic syndrome in classical Hodgkin lymphoma is closely related to the induction of c-mip in Hodgkin-Reed Sternberg cells and podocytes.
abstract: It is currently considered that idiopathic minimal change nephrotic syndrome is an immune-mediated glomerular disease. Its association with classical Hodgkin lymphoma minimal change nephrotic syndrome (cHL-MCNS) suggests a molecular link, which remains to be elucidated. We analyzed the expression of cmaf inducing protein (c-mip) in lymphomatous tissues and kidney biopsy samples of patients with cHL-MCNS (n = 8) and in lymphomatous tissues of patients with isolated cHL (n = 9). Because c-mip affects the regulatory loop involving Fyn, we investigated possible structural defects in this signaling pathway, using laser capture microdissection, reverse transcription polymerase chain reaction, and Western blotting. We found that c-mip was selectively expressed in Hodgkin and Reed-Sternberg (HRS) cells and podocytes of patients with cHL-MCNS but is undetectable in patients with isolated cHL. We demonstrated that c-mip was specifically involved in the negative regulation of early proximal signaling through its interaction with phosphoprotein associated with glycosphingolipid-enriched microdomains and Fyn. We showed that the up-regulation of c-mip in cHL-MCNS was associated with a possible Fyn defect in HRS cells and podocytes. Moreover, we showed that c-mip was up-regulated in Fyn-deficient podocytes. c-mip may be a useful marker of cHL-MCNS and its induction reflects the dysregulation of proximal signaling.
authors.affiliation: Inserm, U955, Equipe 21, Créteil, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
authors.forename: Shao-yu
authors.initials: SY
authors.lastname: Zhang
authors.forename: Christiane
authors.initials: C
authors.lastname: Copie-Bergman
authors.forename: Catherine
authors.initials: C
authors.lastname: Rucker-Martin
authors.forename: Virginie
authors.initials: V
authors.lastname: Ory
authors.forename: Marina
authors.initials: M
authors.lastname: Candelier
authors.forename: Maryse
authors.initials: M
authors.lastname: Baia
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: André
authors.initials: A
authors.lastname: Pawlak
authors.forename: Djillali
authors.initials: D
authors.lastname: Sahali
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D000081247:CSK Tyrosine-Protein Kinase; D002352:Carrier Proteins / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D006689:Hodgkin Disease / Q000150:complications* / Q000378:metabolism; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D042282:Microdissection; D009402:Nephrosis, Lipoid / Q000150:complications* / Q000378:metabolism; D050199:Podocytes / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D019061:src-Family Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540426:CMIP protein, human; D002352:Carrier Proteins; D008565:Membrane Proteins; C498710:PAG1 protein, human; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D019061:src-Family Kinases; C000631346:CSK protein, human