1 3
Int Urol Nephrol
DOI 10.1007/s11255-015-0993-1
NEPHROLOGY - ORIGINAL PAPER
Expression of bone morphogenetic proteins 4, 6 and 7
is downregulated in kidney allografts with interstitial
fibrosis and tubular atrophy
Vesna Furic-Cunko
1
· Petar Kes
1
· Marijana Coric
2
· Tvrtko Hudolin
3
·
Zeljko Kastelan
3
· Nikolina Basic-Jukic
1
Received: 10 December 2014 / Accepted: 20 April 2015
© Springer Science+Business Media Dordrecht 2015
epithelial cells and does not differ between the compared
allografts and control kidney specimens.
Conclusion The intensity and expression pattern of
BMP4, BMP6 and BMP7 in transplanted kidney tissue are
found to be dependent upon the length of the transplanted
period, the clinical indication for transplant nephrectomy
and signs of IFTA in kidney tissue.
Keywords Bone morphogenetic proteins · Chronic graft
dysfunction · Interstitial fibrosis tubular atrophy · Kidney ·
Transplantation · Transplant nephrectomy
Introduction
Bone morphogenetic proteins (BMPs) are pleiotropic
growth factors that regulate growth, differentiation, chemo-
taxis and apoptosis of different cell types [1]. They regulate
kidney development and maintain structure and function
in mature kidneys [2]. In kidney transplant recipients, only
one study of biopsy series investigated the role of BMP7 in
early fibrogenesis activation after transplantation [3]. The
aim of this study is to investigate the connection between
the expression pattern of BMPs in kidney allograft tissue
versus the cause of allograft dysfunction and the subse-
quent need for transplant nephrectomy.
Methods
Tissue samples
Tissue samples from 50 consecutive patients who under-
went graft nephrectomy were obtained at the Department
of Urology of the University Hospital Zagreb, in Zagreb,
Abstract
Purpose Bone morphogenetic proteins (BMPs) are pleio-
tropic growth factors. This paper investigates the connec-
tion between the expression pattern of BMPs in kidney
allograft tissue versus the cause of allograft dysfunction.
Methods The expression pattern of BMP2, BMP4, BMP6
and BMP7 in 50 kidney allografts obtained by transplant
nephrectomy is investigated. Immunohistochemical stain-
ing is semiquantitatively evaluated for intensity to identify
the expression pattern of BMPs in normal and allograft kid-
ney tissues.
Results The expression of BMP4 is unique between dif-
ferent tubular cell types in grafts without signs of fibrosis.
This effect is not found in specimens with high grades of
interstitial fibrosis and tubular atrophy (IFTA). In sam-
ples with IFTA grades II and III, the BMP7 expression is
reduced in a significant fraction of specimens relative to
those without signs of IFTA. The expression pattern of
BMP6 indicates that its activation may be triggered by the
act of transplantation and subsequent reperfusion injury.
The expression of BMP2 is strong in all types of tubular
* Vesna Furic-Cunko
vfcunko@gmail.com
1
Department of Nephrology, Arterial Hypertension, Dialysis
and Transplantation, University Hospital Centre Zagreb,
Kispaticeva 12, 10 000 Zagreb, Croatia
2
Department of Pathology, University Hospital Centre Zagreb,
Kispaticeva 12, 10 000 Zagreb, Croatia
3
Urology Department, University Hospital Centre Zagreb,
Kispaticeva 12, 10 000 Zagreb, Croatia