RGD Reference Report - Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation. - Rat Genome Database

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Distinct in vivo roles of colony-stimulating factor-1 isoforms in renal inflammation.

Authors: Jang, MH  Herber, DM  Jiang, X  Nandi, S  Dai, XM  Zeller, G  Stanley, ER  Kelley, VR 
Citation: Jang MH, etal., J Immunol. 2006 Sep 15;177(6):4055-63.
RGD ID: 7257574
Pubmed: PMID:16951369   (View Abstract at PubMed)

CSF-1, the major regulator of macrophage (Mphi) development, has three biologically active isoforms: a membrane-spanning, cell surface glycoprotein, a secreted glycoprotein, and a secreted proteoglycan. We hypothesized that there are shared and unique roles of individual CSF-1 isoforms during renal inflammation. To test this, we evaluated transgenic mice only expressing the cell surface or precursors of the secreted CSF-1 isoforms for Mphi accumulation, activation, and Mphi-mediated tubular epithelial cell (TEC) apoptosis during unilateral ureteral obstruction. The only difference between secreted proteoglycan and secreted glycoprotein CSF-1 isoforms is the presence (proteoglycan) or absence (glycoprotein) of an 18-kDa chondroitin sulfate glycosaminoglycan. We report that 1) cell surface CSF-1 isoform is sufficient to restore Mphi accumulation, activation, and TEC apoptosis to wild-type levels and is substantially more effective than the secreted CSF-1 isoforms; 2) the chondroitin sulfate glycosaminoglycan facilitates Mphi accumulation, activation, and TEC apoptosis; 3) increasing the level of secreted proteoglycan CSF-1 in serum amplifies renal inflammation; and 4) cell-cell contact is required for Mphi to up-regulate CSF-1-dependent expression of IFN-gamma. Taken together, we have identified central roles for the cell surface CSF-1 and the chondroitin sulfate chain on secreted proteoglycan CSF-1 during renal inflammation.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ureteral obstruction  ISOCsf1 (Mus musculus)7257574; 7257574 RGD 
ureteral obstruction  ISOCsf1r (Mus musculus)7257574; 7257574protein:increased expression:kidney and macrophageRGD 
ureteral obstruction  IMP 7257574 RGD 
ureteral obstruction  IEP 7257574protein:increased expression:kidney and macrophageRGD 

Objects Annotated

Genes (Rattus norvegicus)
Csf1  (colony stimulating factor 1)
Csf1r  (colony stimulating factor 1 receptor)

Genes (Mus musculus)
Csf1  (colony stimulating factor 1 (macrophage))
Csf1r  (colony stimulating factor 1 receptor)

Genes (Homo sapiens)
CSF1  (colony stimulating factor 1)
CSF1R  (colony stimulating factor 1 receptor)

Additional Information