PMID- 18923384
OWN - NLM
STAT- MEDLINE
DCOM- 20090518
LR  - 20090227
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 75
IP  - 6
DP  - 2009 Mar
TI  - An in vitro model of light chain deposition disease.
PG  - 634-45
LID - 10.1038/ki.2008.504 [doi]
AB  - Nodular glomerulosclerosis results from increased deposition of extracellular 
      matrix proteins and monotypic light chains. The inability of mesangial cells to 
      degrade abnormal levels of tenascin-C--along with the increased expression of 
      some growth factors such as platelet-derived growth factor (PDGF) and 
      transforming growth factor-beta (TGF-beta)--is crucial to the pathogenesis of 
      light chain deposition disease (LCDD). In order to study the molecular processes 
      contributing to LCDD, we grew mesangial cells in three-dimensional matrices and 
      incubated the cells with free light chains purified from the urine of patients 
      with biopsy-proven LCDD, immunoglobulin-associated amyloid deposits, or myeloma 
      cast nephropathy. Light chains of the latter two cohorts served as controls. 
      Mesangial cells incubated with light chains from patients with LCDD show a 
      significant increase in tenascin-C expression, centrally located within newly 
      formed nodules, along with increased expression of PDGF and TGF-betas, compared 
      to mesangial cells incubated with control light chains. There was less 
      extracellular MMP-7 even though its intracellular expression is markedly 
      increased compared to the control. Addition of active MMP-7 degraded this excess 
      tenascin-C in vitro, a process that could be prevented by an exogenous MMP 
      inhibitor. Our in vitro model recapitulates in vivo findings in patients with 
      LCDD, thus allowing definition of the sequential pathologic processes associated 
      with glomerulopathic light chain interactions with mesangial cells.
FAU - Keeling, John
AU  - Keeling J
AD  - Department of Pathology, Saint Louis University Health Sciences Center, Saint 
      Louis, Missouri, USA.
FAU - Herrera, Guillermo A
AU  - Herrera GA
LA  - eng
PT  - Journal Article
DEP - 20081015
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Immunoglobulin Light Chains)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (Tenascin)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 3.4.24.23 (Matrix Metalloproteinase 7)
SB  - IM
CIN - Kidney Int. 2009 Mar;75(6):574-6. PMID: 19247379
MH  - Case-Control Studies
MH  - Cells, Cultured
MH  - Diabetic Nephropathies/etiology/*pathology
MH  - Humans
MH  - Immunoglobulin Light Chains/*pharmacology
MH  - Matrix Metalloproteinase 7/analysis
MH  - Mesangial Cells/pathology
MH  - Platelet-Derived Growth Factor/analysis
MH  - Tenascin/analysis
MH  - Transforming Growth Factor beta/analysis
EDAT- 2008/10/17 09:00
MHDA- 2009/05/19 09:00
CRDT- 2008/10/17 09:00
PHST- 2008/10/17 09:00 [pubmed]
PHST- 2009/05/19 09:00 [medline]
PHST- 2008/10/17 09:00 [entrez]
AID - S0085-2538(15)53745-9 [pii]
AID - 10.1038/ki.2008.504 [doi]
PST - ppublish
SO  - Kidney Int. 2009 Mar;75(6):634-45. doi: 10.1038/ki.2008.504. Epub 2008 Oct 15.