Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: the role of mesangial cell progenitors.
The pathologic hallmarks of diabetic nephropathy are excess mesangial extracellular matrix (ECM) and mesangial cell proliferation. We previously showed that mesangial cell phenotypic changes play an important role in the pathogenesis of diabetic nephropathy. We concluded that phenotypic changes were present in bone marrow (BM)-derived mesangial cell progenitors, as transplantation of BM from db/db mice, a model of type 2 diabetic nephropathy, transferred the db genotype and a nephropathy phenotype to naive B6 mice recipients. The recipients did not develop diabetes; however, they did develop albuminuria and glomerular lesions mirroring those in the donors (i.e., glomerular hypertrophy, increased ECM, and increased cell number with cell proliferation). We found that matrix metalloproteinase 2 (MMP-2) facilitated invasion of the mesangial cells into ECM and proliferation in vitro. Thus, increased MMP-2 activity in db/db mesangial cell progenitors may partially explain increased mesangial cell repopulation and proliferation in B6 recipients of db/db BM. In summary, BM-derived mesangial cell progenitors may play a crucial role in the development and progression of ECM accumulation and mesangial cell proliferation in this model of diabetic nephropathy in type 2 diabetes.
Zheng
Feng
F
University of Miami School of Medicine, Rosenstiel Medical Science Bldg., Rm. 1023A, 1600 NW 10th Ave., Miami, FL, 33136, USA. fzheng@med.miami.edu
Cornacchia
Flavia
F
Schulman
Ivonne
I
Banerjee
Anita
A
Cheng
Qing-Li
QL
Potier
Mylene
M
Plati
Anna Rita
AR
Berho
Mariana
M
Elliot
Sharon J
SJ
Li
Jie
J
Fornoni
Alessia
A
Zang
Yun-Juan
YJ
Zisman
Ariel
A
Striker
Liliane J
LJ
Striker
Gary E
GE
D000419:Albuminuria / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D001786:Blood Glucose; D016026:Bone Marrow Transplantation; D002455:Cell Division; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000473:pathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology*; D005260:Female; D005920:Glomerular Mesangium / Q000378:metabolism / Q000473:pathology*; D007328:Insulin / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D013234:Stem Cells / Q000166:cytology
D001786:Blood Glucose; D007328:Insulin; D020778:Matrix Metalloproteinase 2