TY - JOUR
T1 - Macrophages promote cyst growth in polycystic kidney disease
AU - Karihaloo, Anil
AU - Koraishy, Farrukh
AU - Huen, Sarah
AU - Lee, Yashang
AU - Merrick, David
AU - Caplan, Michael J.
AU - Somlo, Stefan
AU - Cantley, Lloyd G.
PY - 2011/10
Y1 - 2011/10
N2 - Polycystic kidney disease (PKD) exhibits an inflammatory component, but the contribution of inflammation to cyst progression is unknown. Macrophages promote the proliferation of tubular cells following ischemic injury, suggesting that they may have a role in cystogenesis. Furthermore, cultured Pkd1-deficient cells express the macrophage chemoattractants Mcp1 and Cxcl16 and stimulate macrophage migration. Here, in orthologous models of both PKD1 and PKD2, abnormally large numbers of alternatively activated macrophages surrounded the cysts. To determine whether pericystic macrophages contribute to the proliferation of cyst-lining cells, we depleted phagocytic cells from Pkd1 fl/fl;Pkhd1-Cre mice by treating with liposomal clodronate from postnatal day 10 until day 24. Compared with vehicle-treated controls, macrophage-depleted mice had a significantly lower cystic index, reduced proliferation of cyst-lining cells, better-preserved renal parenchyma, and improved renal function. In conclusion, these data suggest that macrophages home to cystic areas and contribute to cyst growth. Interruption of these homing and proliferative signals could have therapeutic potential for PKD.
AB - Polycystic kidney disease (PKD) exhibits an inflammatory component, but the contribution of inflammation to cyst progression is unknown. Macrophages promote the proliferation of tubular cells following ischemic injury, suggesting that they may have a role in cystogenesis. Furthermore, cultured Pkd1-deficient cells express the macrophage chemoattractants Mcp1 and Cxcl16 and stimulate macrophage migration. Here, in orthologous models of both PKD1 and PKD2, abnormally large numbers of alternatively activated macrophages surrounded the cysts. To determine whether pericystic macrophages contribute to the proliferation of cyst-lining cells, we depleted phagocytic cells from Pkd1 fl/fl;Pkhd1-Cre mice by treating with liposomal clodronate from postnatal day 10 until day 24. Compared with vehicle-treated controls, macrophage-depleted mice had a significantly lower cystic index, reduced proliferation of cyst-lining cells, better-preserved renal parenchyma, and improved renal function. In conclusion, these data suggest that macrophages home to cystic areas and contribute to cyst growth. Interruption of these homing and proliferative signals could have therapeutic potential for PKD.
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U2 - 10.1681/ASN.2011010084
DO - 10.1681/ASN.2011010084
M3 - Article
C2 - 21921140
AN - SCOPUS:80053557318
SN - 1046-6673
VL - 22
SP - 1809
EP - 1814
JO - Journal of the American Society of Nephrology
JF - Journal of the American Society of Nephrology
IS - 10
ER -