Inhibition of endogenous BMP in the glomerulus leads to mesangial matrix expansion.
Bone morphogenetic protein7 (BMP7) attenuates renal tubular and interstitial damage in a variety of experimental models. The function of BMP in the glomerulus is, however, not well understood. In the present study, we generated transgenic mice carrying cDNA for noggin, an endogenous inhibitor of BMPs, driven by the podocyte-specific promoter nephrin. Transgenic founder mice could be divided into two groups based on gross histological analyses at 2 months of age. One group was characterized by the presence of cystic glomeruli with collapsed capillary tufts and a decrease in mesangial cell number, representing a developmental defect during glomerular morphogenesis ("cystic" Tg mice). In contrast, the kidneys appeared to be normal in the other group ("non-cystic" Tg mice). In both groups, however, massive mesangial expansion developed at 10 months of age. The lesion was characterized by the accumulation of fibronectin, but not type I collagen, type IV collagen or laminin. This phenotype is similar to the fibronectin nephropathy. These results suggest that endogenous BMP can have an important role in regulating glomerular structural homeostasis.
Miyazaki
Yoichi
Y
Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan. yoichimiyazaki@jikei.ac.jp
Ueda
Hiroyuki
H
Yokoo
Takashi
T
Utsunomiya
Yasunori
Y
Kawamura
Tetsuya
T
Matsusaka
Taiji
T
Ichikawa
Iekuni
I
Hosoya
Tatsuo
T
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics; D005109:Extracellular Matrix / Q000187:drug effects* / Q000473:pathology; D005260:Female; D005920:Glomerular Mesangium / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000502:physiology*; D017403:In Situ Hybridization; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000378:metabolism; D000099176:Noggin Protein
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; D000099176:Noggin Protein; C113267:nephrin