TY - JOUR
T1 - Tubular epithelial syndecan-1 maintains renal function in murine ischemia/reperfusion and human transplantation
AU - Celie, Johanna W. A. M.
AU - Katta, Kiran K.
AU - Adepu, Saritha
AU - Melenhorst, Wynand B. W. H.
AU - Reijmers, Rogier M.
AU - Slot, Edith M.
AU - Beelen, Robert H. J.
AU - Spaargaren, Marcel
AU - Ploeg, Rutger J.
AU - Navis, Gerjan
AU - Homan van der Heide, J. J.
AU - van Dijk, Marcory C. R. F.
AU - van Goor, Harry
AU - van den Born, Jacob
PY - 2012
Y1 - 2012
N2 - Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control. Increased epithelial syndecan-1 in allografts correlated with low proteinuria and serum creatinine, less interstitial inflammation, less tubular atrophy, and prolonged allograft survival. Knockdown of syndecan-1 in human tubular epithelial cells in vitro reduced cell proliferation. Selective binding of growth factors suggests that syndecan-1 may promote epithelial restoration. Bilateral renal ischemia/reperfusion in syndecan-1-deficient mice resulted in increased initial renal failure and tubular injury compared with wild-type mice. Macrophage and myofibroblast numbers, tubular damage, and plasma urea levels were increased, and tubular proliferation reduced in the kidneys of syndecan-1 deficient compared with wild-type mice 14 days following injury. Hence syndecan-1 promotes tubular survival and repair in murine ischemia/reperfusion injury and correlates with functional improvement in human renal allograft transplantation. Kidney International (2012) 81, 651-661; doi:10.1038/ki.2011.425; published online 11 January 2012
AB - Syndecan-1, a heparan sulfate proteoglycan, has an important role in wound healing by binding several growth factors and cytokines. As these processes are also crucial in damage and repair after renal transplantation, we examined syndecan-1 expression in human control kidney tissue, renal allograft protocol biopsies, renal allograft biopsies taken at indication, and non-transplant interstitial fibrosis. Syndecan-1 expression was increased in tubular epithelial cells in renal allograft biopsies compared with control. Increased epithelial syndecan-1 in allografts correlated with low proteinuria and serum creatinine, less interstitial inflammation, less tubular atrophy, and prolonged allograft survival. Knockdown of syndecan-1 in human tubular epithelial cells in vitro reduced cell proliferation. Selective binding of growth factors suggests that syndecan-1 may promote epithelial restoration. Bilateral renal ischemia/reperfusion in syndecan-1-deficient mice resulted in increased initial renal failure and tubular injury compared with wild-type mice. Macrophage and myofibroblast numbers, tubular damage, and plasma urea levels were increased, and tubular proliferation reduced in the kidneys of syndecan-1 deficient compared with wild-type mice 14 days following injury. Hence syndecan-1 promotes tubular survival and repair in murine ischemia/reperfusion injury and correlates with functional improvement in human renal allograft transplantation. Kidney International (2012) 81, 651-661; doi:10.1038/ki.2011.425; published online 11 January 2012
U2 - https://doi.org/10.1038/ki.2011.425
DO - https://doi.org/10.1038/ki.2011.425
M3 - Article
C2 - 22237752
SN - 0085-2538
VL - 81
SP - 651
EP - 661
JO - Kidney International
JF - Kidney International
IS - 7
ER -