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
- 6 May 2010
- journal article
- research article
- Published by American Society of Hematology in Blood
- Vol. 115 (18), 3756-3762
- https://doi.org/10.1182/blood-2009-11-251132
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.Keywords
This publication has 31 references indexed in Scilit:
- C-mip interacts physically with RelA and inhibits nuclear factor kappa B activityMolecular Immunology, 2009
- Rituximab treatment for severe steroid- or cyclosporine-dependent nephrotic syndrome: a multicentric series of 22 casesPediatric Nephrology, 2008
- PAG-Associated FynT Regulates Calcium Signaling and Promotes Anergy in T LymphocytesMolecular and Cellular Biology, 2007
- Membrane and juxtamembrane targeting by PH and PTB domainsBiochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2006
- Nephrin ectodomain engagement results in Src kinase activation, nephrin phosphorylation, Nck recruitment, and actin polymerizationJCI Insight, 2006
- Bigenic mouse models of focal segmental glomerulosclerosis involving pairwise interaction of CD2AP, Fyn, and synaptopodinJCI Insight, 2006
- Follicular B helper T cells in antibody responses and autoimmunityNature Reviews Immunology, 2005
- Truncation of C-mip (Tc-mip), a New Proximal Signaling Protein, Induces c-maf Th2 Transcription Factor and Cytoskeleton ReorganizationThe Journal of Experimental Medicine, 2003
- Phosphoprotein Associated with Glycosphingolipid-Enriched Microdomains (Pag), a Novel Ubiquitously Expressed Transmembrane Adaptor Protein, Binds the Protein Tyrosine Kinase Csk and Is Involved in Regulation of T Cell ActivationThe Journal of Experimental Medicine, 2000
- Paraneoplastic glomerulopathies: New insights into an old entityKidney International, 1999