CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy (2024)

Falke, L. L., Leeuwis, J. W., Lyons, K. M., Mummery, C. L., Nguyen, T. Q., & Goldschmeding, R. (2017). CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy. Journal of Cell Communication and Signaling, 11(1), 39-48. https://doi.org/10.1007/s12079-016-0358-2

Falke, Lucas L. ; Leeuwis, Jan Willem ; Lyons, Karen M. et al. / CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy. In: Journal of Cell Communication and Signaling. 2017 ; Vol. 11, No. 1. pp. 39-48.

@article{0736ff49d1724ba2b92f23094496affd,

title = "CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy",

abstract = "Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction w(UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice). We also analysed the impact of rhBMP7 treatment on severity of the UUO phenotype, on TGFβ signaling, and on expression of CCN2 (CTGF). Despite profound protective effects with respect to morphological damage, macrophage infiltration, and fibrosis, no significant difference in GFP-expression was observed upon rhBMP7 administration. Also TGFβ signalling was similar in rhBMP7 and vehicle treated mice, but CCN2 expression in obstructed kidneys was significantly reduced by rhBMP7 treatment. Of note, in heterozygous CCN2 mice (CCN2+/−) treatment with rhBMP7 did not (further) reduce the severity of kidney damage in the UUO-model. These data suggest that protection against obstructive nephropathy by exogenous rhBMP7 treatment relies primarily on non-canonical BMP signaling, and may be mediated in large part by downregulation of CCN2 expression.",

keywords = "BMP7, CCN2, CKD, Kidney, TGFβ, UUO",

author = "Falke, {Lucas L.} and Leeuwis, {Jan Willem} and Lyons, {Karen M.} and Mummery, {Christine L.} and Nguyen, {Tri Q.} and Roel Goldschmeding",

year = "2017",

month = mar,

day = "1",

doi = "10.1007/s12079-016-0358-2",

language = "English",

volume = "11",

pages = "39--48",

journal = "Journal of Cell Communication and Signaling",

issn = "1873-9601",

publisher = "Springer Netherlands",

number = "1",

}

Falke, LL, Leeuwis, JW, Lyons, KM, Mummery, CL, Nguyen, TQ & Goldschmeding, R 2017, 'CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy', Journal of Cell Communication and Signaling, vol. 11, no. 1, pp. 39-48. https://doi.org/10.1007/s12079-016-0358-2

CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy. / Falke, Lucas L.; Leeuwis, Jan Willem ; Lyons, Karen M. et al.
In: Journal of Cell Communication and Signaling, Vol. 11, No. 1, 01.03.2017, p. 39-48.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy

AU - Falke, Lucas L.

AU - Leeuwis, Jan Willem

AU - Lyons, Karen M.

AU - Mummery, Christine L.

AU - Nguyen, Tri Q.

AU - Goldschmeding, Roel

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction w(UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice). We also analysed the impact of rhBMP7 treatment on severity of the UUO phenotype, on TGFβ signaling, and on expression of CCN2 (CTGF). Despite profound protective effects with respect to morphological damage, macrophage infiltration, and fibrosis, no significant difference in GFP-expression was observed upon rhBMP7 administration. Also TGFβ signalling was similar in rhBMP7 and vehicle treated mice, but CCN2 expression in obstructed kidneys was significantly reduced by rhBMP7 treatment. Of note, in heterozygous CCN2 mice (CCN2+/−) treatment with rhBMP7 did not (further) reduce the severity of kidney damage in the UUO-model. These data suggest that protection against obstructive nephropathy by exogenous rhBMP7 treatment relies primarily on non-canonical BMP signaling, and may be mediated in large part by downregulation of CCN2 expression.

AB - Treatment with rhBMP7 exerts profound protective effects in a wide variety of experimental models of renal disease. However, little is known about how these protective effects are mediated, and which cells in the kidney are targeted by exogenous rhBMP7 treatment. To determine if rhBMP7 increases glomerular and tubulointerstitial canonical BMP signaling, we performed Unilateral Ureteral Obstruction w(UUO, a widely used obstructive nephropathy model) in mice reporting transcriptional activity downstream of canonical BMP signaling by the expression of GFP under the BMP Responsive Element of the Id1 promoter (BRE:gfp mice). We also analysed the impact of rhBMP7 treatment on severity of the UUO phenotype, on TGFβ signaling, and on expression of CCN2 (CTGF). Despite profound protective effects with respect to morphological damage, macrophage infiltration, and fibrosis, no significant difference in GFP-expression was observed upon rhBMP7 administration. Also TGFβ signalling was similar in rhBMP7 and vehicle treated mice, but CCN2 expression in obstructed kidneys was significantly reduced by rhBMP7 treatment. Of note, in heterozygous CCN2 mice (CCN2+/−) treatment with rhBMP7 did not (further) reduce the severity of kidney damage in the UUO-model. These data suggest that protection against obstructive nephropathy by exogenous rhBMP7 treatment relies primarily on non-canonical BMP signaling, and may be mediated in large part by downregulation of CCN2 expression.

KW - BMP7

KW - CCN2

KW - CKD

KW - Kidney

KW - TGFβ

KW - UUO

UR - http://www.scopus.com/inward/record.url?scp=84991784015&partnerID=8YFLogxK

U2 - 10.1007/s12079-016-0358-2

DO - 10.1007/s12079-016-0358-2

M3 - Article

C2 - 27766493

AN - SCOPUS:84991784015

SN - 1873-9601

VL - 11

SP - 39

EP - 48

JO - Journal of Cell Communication and Signaling

JF - Journal of Cell Communication and Signaling

IS - 1

ER -

Falke LL, Leeuwis JW, Lyons KM, Mummery CL, Nguyen TQ, Goldschmeding R. CCN2 reduction mediates protective effects of BMP7 treatment in obstructive nephropathy. Journal of Cell Communication and Signaling. 2017 Mar 1;11(1):39-48. doi: 10.1007/s12079-016-0358-2