Bone morphogenetic protein-7 expression and activity in the human adult normal kidney is predominantly localized to the distal nephron.
Bone morphogenetic protein-7 (BMP)-7 plays an important role during fetal kidney development. In the adult, BMP-7 is most strongly expressed in the kidney compared to other organs, but the exact expression pattern as well as the function of BMP-7 is unclear. The major aim of the present study was to define which parts of the human kidney do physiologically express BMP-7 and which cells appear to be targets of BMP activity by showing phosphorylated BMP-receptor-associated Smads 1, 5, or 8 and inhibitor of differentiation factor 1 (ID1) expression. BMP-7 expression was localized by immunohistology to the epithelia of the distal tubule as well as the collecting ducts (CDs). Phospho-Smads 1/5/8 and ID1 expression largely colocalized with BMP-7 and was also localized in the epithelia of the distal tubule and the CDs. This was confirmed by polymerase chain reaction-based mRNA expression analysis. In vitro, proximal tubular cells (PTCs) expressed BMP receptors and BMP-receptor-associated Smads and were reactive to BMP-7. Our data indicate that BMP-7 expression in the adult human kidney appears to be more restricted than in the fetal situation and predominantly found in the distal nephron. Also, evidence of in vivo BMP signalling (i.e. phospho-Smads and ID1 expression) was found there. These findings suggest that BMP-7 plays a physiological role mostly in this part of the kidney. Still, as reported previously, PTCs are responsive to BMP-7, but presumably not in an autocrine or paracrine mode in normal adult kidneys.
Wetzel
P
P
Osteoarticular and Arthritis Research, Department of Pathology, University of Erlangen-Nürnberg, Erlangen, FRG.
Haag
J
J
Câmpean
V
V
Goldschmeding
R
R
Atalla
A
A
Amann
K
K
Aigner
T
T
D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism*; D002460:Cell Line; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism; D007686:Kidney Tubules, Distal / Q000166:cytology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051898:Smad1 Protein / Q000235:genetics / Q000378:metabolism; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D051904:Smad8 Protein / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism*
C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; C497453:ID1 protein, human; D051798:Inhibitor of Differentiation Protein 1; D012333:RNA, Messenger; C497399:SMAD1 protein, human; C497797:SMAD5 protein, human; C107514:SMAD9 protein, human; D051898:Smad1 Protein; D051902:Smad5 Protein; D051904:Smad8 Protein; D016212:Transforming Growth Factor beta