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ID 113757
Title Alternative
BMP4 in Diabetic Nephropathy
Author
Fujita, Yui Tokushima University
Kangawa, Yumi Tokushima University
Keywords
BMP4
diabetic nephropathy
podocyte
apotosis
mesangial expansion
Content Type
Journal Article
Description
Podocyte injury and loss have been indicated as constituting the crucial pathogenesis of glomerular injury ; however, it remains necessary to elucidate the detailed molecular mechanisms and cell-to-cell response because multiple factors may cause podocyte injury. In the glomerulus, three kinds of cells (endothelial, mesangial, and parietal epithelial) react to podocyte injury. Endothelial and mesangial cells are connected with podocyte cells across the glomerular basement membrane. However, the detailed mechanisms regarding the interaction of the mesangium and podocyte injury are unclear.
Diabetic nephropathy is characterized by mesangial matrix expansion caused by an excessive deposition of extracellular matrix proteins in the mesangial area, which can be observed through the increased expression of type IV collagen. We have shown that bone morphogenetic protein 4 (BMP4) signaling leads to the glomerular changes characteristic of this disorder. To analyze the effect of BMP4 was investigated in vitro and in vivo using streptozotocin (STZ)-induced and Bmp4 heterozygous knockout (Bmp4+/-) diabetic mice or podocyte-specific Bmp4 knockout mice, and Bmp4-induced or podocyte-specific transgenic mice. BMP4 positive area and mesangial area fraction showed positively correlation. Furthermore, mesangial area fraction was significantly and negatively correlated with,WT1-positive cell number, and nephrin-positive area.
We also demonstrated that the induction of podocyte apoptosis by BMP4 may be mediated by p38 activation and that of caspase 3 through cleavage. In mesangial cells, BMP4 stimulation also induced phosphorylation of p38 and Smad1 and increased cleaved caspase 3, with similar significant inhibition of Smad1 activation and decreased cleaved caspase 3 mediated by dorsomorphin.
These data suggest that the BMP4 signaling pathway plays important roles for the development of both podocyte injury and mesangial expansion in diabetic nephropathy.
Journal Title
Shikoku Acta Medica
ISSN
00373699
NCID
AN00102041
Publisher
徳島医学会
Volume
75
Issue
1-2
Start Page
55
End Page
62
Sort Key
55
Published Date
2019-04-25
FullText File
language
jpn
TextVersion
Publisher
departments
Medical Sciences
University Hospital