Abstract
The length of primary cilia is associated with normal cell and organ function. In the kidney, the change of functional cilia length/mass is associated with various diseases such as ischemia/reperfusion injury, polycystic kidney disease, and congenital solitary kidney. Here, we investigate whether renal mass reduction affects primary cilia length and function. To induce renal mass reduction, mice were subjected to unilateral nephrectomy (UNx). UNx increased kidney weight and superoxide formation in the remaining kidney. Primary cilia were elongated in proximal tubule cells, collecting duct cells and parietal cells of the remaining kidney. Mn(III) Tetrakis (1-methyl-4-pyridyl) porphyrin (MnTMPyP), an antioxidant, reduced superoxide formation in UNx-mice and prevented the elongation of primary cilia. UNx increased the expression of phosphorylated ERK, p21, and exocyst complex members Sec8 and Sec10, in the remaining kidney, and these increases were prevented by MnTMPyP. In MDCK, a kidney tubular epithelial cell line, cells, low concentrations of H2O2 treatment elongated primary cilia. This H2O2-induced elongation of primary cilia was also prevented by MnTMPyP treatment. Taken together, these data demonstrate that kidney compensation, induced by a reduction of renal mass, results in primary cilia elongation, and this elongation is associated with an increased production of reactive oxygen species (ROS).
Highlights
In the present study we investigated if and how renal mass reduction by UNx regulates primary cilia length in the remaining kidney
We find, for the first time, that 1) UNx results in the elongation of primary cilia in the tubular epithelial and parietal cells of the remaining kidney, 2) the elongation of primary cilia after UNx is inhibited by antioxidant treatment, and 3) ROS elongates primary cilia in the cultured tubular cells and this ROS-induced elongation is prevented by antioxidant treatment
These findings indicate that elongation of primary cilia in the remaining kidney cells after renal mass reduction is an adaptive response of kidney epithelial to compensate for increased renal flow in the remaining kidney following UNx
Summary
In the present study we investigated if and how renal mass reduction by UNx regulates primary cilia length in the remaining kidney. We report that UNx elongates primary cilia length in the remaining kidney, and that this elongation is mediated by ROS. For the first time, that increased ROS, even at low levels, elongates primary cilia, suggesting that the regulation of primary cilia length may be necessary for the compensation and maintenance of renal function following a reduction in total renal mass. We suggest that UNx is an outstanding model for the study of primary cilia, as there is no direct pathologic insult, which is not the case in ischemic or nephrotoxic injury models
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