Renal primary cilia lengthen in the progression of diabetic kidney disease

Abstract

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease, and its early pathogenesis is critical. Shear stress caused by glomerular hyperfiltration contributes to the initiation of kidney injury in diabetes. The primary cilium of renal tubular epithelial cells (RTECs) is an important mechanical force sensor of shear stress and regulates energy metabolism homeostasis in RTECs to ensure energy supply for reabsorption functions, but little is known about the alterations in the renal cilium number and length during the progression of DKD. Here, we demonstrate that aberrant ciliogenesis and dramatic increase in the cilium length, the number of ciliated cells, and the length of cilia are positively correlated with the DKD class in the kidney biopsies of DKD patients by super-resolution imaging and appropriate statical analysis methods. This finding was further confirmed in STZ-induced or db/db diabetic mice. These results suggest that the number and length of renal cilia may be clinically relevant indicators and that cilia will be attractive therapeutic targets for DKD.

Mechanisms underlying morphological and functional changes of cilia in fibroblasts derived from patients bearing ARL3T31A and ARL3T31A/C118F mutations

“…The length of the cilia, which are formed by differentiated cells or single‐celled organisms, is relatively constant and plays a crucial role in maintaining normal ciliary function in motility and signal transduction. Defects in cilia length can lead to a variety of ciliary illnesses, such as diabetic kidney disease, obesity, 19 polycystic kidney disease, 20 age‐related diseases, 21 and BBS 22 . To investigate the association between mutations (ARL3 T31A and ARL3 T31A/C118F ) and cilia length, we measured the ciliary length of ARL3 WT , ARL3 T31A , and ARL3 T31A/C118F fibroblasts using ARL13B and acetylated α‐tubulin antibody to identify primary cilia.…”

Increased ER stress by depletion of PDIA6 impairs primary ciliogenesis and enhances sensitivity to ferroptosis in kidney cells

“…Pdia6 +/− mice displayed glomerular abnormalities that are suggestive of glomerulosclerosis. As glomerulosclerosis progresses, the abnormalities in cilia become more apparent (41). While the exact mechanisms linking ferroptosis and cilia are still unclear, these findings could provide insights into future renal disease treatment.…”

The roles of gut microbiota and its metabolites in diabetic nephropathy

“…Meanwhile, ET-1 can also increase the glomerular permeability by targeting its receptor, resulting in the aggravating albuminuria and DN progression ( Ergul, 2011 ). The mechanical strain and shear stress, resulting from altered hemodynamics, lead to endothelial cell and epithelial cell injury, which accelerates the occurrence and development of proteinuria ( Bai et al, 2022 ).…”