Primary cilium in kidney development, function and disease

Abstract

The primary cilium is a hair-like, microtubule-based organelle that is covered by the cell membrane and extends from the surface of most vertebrate cells. It detects and translates extracellular signals to direct various cellular signaling pathways to maintain homeostasis. It is mainly distributed in the proximal and distal tubules and collecting ducts in the kidney. Specific signaling transduction proteins localize to primary cilia. Defects in cilia structure and function lead to a class of diseases termed ciliopathies. The proper functioning of primary cilia is essential to kidney organogenesis and the maintenance of epithelial cell differentiation and proliferation. Persistent cilia dysfunction has a role in the early stages and progression of renal diseases, such as cystogenesis and acute tubular necrosis (ATN). In this review, we focus on the central role of cilia in kidney development and illustrate how defects in cilia are associated with renal disease progression.

Editorial: Advances in the research of diabetic nephropathy, volume II

“…In humans, they showed that the number of ciliated cells and the length of cilia are positively correlated with the diabetic kidney disease class in the kidney biopsies of the patients with diabetic kidney disease. These results are consistent with those of STZ-injected mice and db/db mice ( 6 ). The researchers speculated that HDAC6-dependent tubulin deacetylation was inhibited in renal tubular epithelial cells in diabetic kidney disease ( 6 ).…”

“…These results are consistent with those of STZ-injected mice and db/db mice ( 6 ). The researchers speculated that HDAC6-dependent tubulin deacetylation was inhibited in renal tubular epithelial cells in diabetic kidney disease ( 6 ). They also suggested that aberrant ciliogenesis may influence mitochondrial biogenesis and fatty acid β oxidation, accelerating renal fibrosis.…”

“…In polycystic kidney disease, cilia are absent. Bai et al focused on the role of renal primary cilia lengthening in the development of diabetic kidney disease (6). In humans, they showed that the number of ciliated cells and the length of cilia are positively correlated with the diabetic kidney disease class in the kidney biopsies of the patients with diabetic kidney disease.…”

Nephronophthisis-associated FBW7 mediates cyst-dependent decline of renal function in ADPKD

“…Thus, we utilized ciliary length as a phenotypic read-out assay to identify cell types of genetic interactions between Pkd1 and Fbxw7 across different kidney tubules. Notably, ciliary length is a sensitive measure, particularly relevant during postnatal development and in the context of ADPKD 31 . We found a significant elongation of primary cilia in epithelial cells of proximal tubules of UbcCre ERT2 ;Pkd1 f/f animals, whereas UbcCre ERT2 ;Pkd1 f/f ;Fbxw7 f/f animals exhibited a normalization of ciliary length.…”

Tubular obstruction induced polycystin upregulation is pro-fibrotic and induced a severe cystic phenotype in adult mice with autosomal dominant polycystic kidney disease: the coexistence of polycystin loss and gain function in ADPKD

“…Polcystin-1 (encoded by PKD1 gene) and polycystin-2 (encoded by PKD2 gene) form a transmembrane complex and are located in the primary cilia functioning as a calcium channel, which can sense external stimuli such as growth factors, chemical or mechanic stress (6). Mutations in ciliary genes responsible for the assembly of primary cilia (such as kinesin family member 3A, KIF3A) can also induce cystogenesis in mouse kidneys (7). Accumulating evidence show that ciliary proteins are implicated in the development or disease condition of other organs, for example, bone development and blood pressure control (8)(9)(10)(11).…”