Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: The role of mesangial cell progenitors

Feng Zheng, Flavia Cornacchia, Ivonne H Schulman, Anita Banerjee, Qing Li Cheng, Mylene Potier, Anna Rita Plati, Mariana Berho, Sharon Elliot, Jie Li, Alessia Fornoni, Yun Juan Zang, Ariel Zisman, Liliane J. Striker, Gary E. Striker

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Abstract

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.

Original languageEnglish
Pages (from-to)2420-2427
Number of pages8
JournalDiabetes
Volume53
Issue number9
DOIs
StatePublished - Sep 1 2004

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Albuminuria
Mesangial Cells
Bone Marrow
Diabetic Nephropathies
Cell Proliferation
Extracellular Matrix
Matrix Metalloproteinase 2
Glomerular Mesangium
Bone Marrow Transplantation
Type 2 Diabetes Mellitus
Hypertrophy
Cell Count
Genotype
Phenotype

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow : The role of mesangial cell progenitors. / Zheng, Feng; Cornacchia, Flavia; Schulman, Ivonne H; Banerjee, Anita; Cheng, Qing Li; Potier, Mylene; Rita Plati, Anna; Berho, Mariana; Elliot, Sharon; Li, Jie; Fornoni, Alessia; Zang, Yun Juan; Zisman, Ariel; Striker, Liliane J.; Striker, Gary E.

In: Diabetes, Vol. 53, No. 9, 01.09.2004, p. 2420-2427.

Research output: Contribution to journalArticle

Zheng, F, Cornacchia, F, Schulman, IH, Banerjee, A, Cheng, QL, Potier, M, Rita Plati, A, Berho, M, Elliot, S, Li, J, Fornoni, A, Zang, YJ, Zisman, A, Striker, LJ & Striker, GE 2004, 'Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow: The role of mesangial cell progenitors', Diabetes, vol. 53, no. 9, pp. 2420-2427. https://doi.org/10.2337/diabetes.53.9.2420
Zheng, Feng ; Cornacchia, Flavia ; Schulman, Ivonne H ; Banerjee, Anita ; Cheng, Qing Li ; Potier, Mylene ; Rita Plati, Anna ; Berho, Mariana ; Elliot, Sharon ; Li, Jie ; Fornoni, Alessia ; Zang, Yun Juan ; Zisman, Ariel ; Striker, Liliane J. ; Striker, Gary E. / Development of albuminuria and glomerular lesions in normoglycemic B6 recipients of db/db mice bone marrow : The role of mesangial cell progenitors. In: Diabetes. 2004 ; Vol. 53, No. 9. pp. 2420-2427.
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