Bardet–Biedl syndrome highlights the major role of the primary cilium in efficient water reabsorption

Abstract

Studies of the primary cilium, now known to be present in all cells, have undergone a revolution, in part, because mutation of many of its proteins causes a large number of diseases, including cystic kidney disease. Bardet-Biedl syndrome (BBS) is an inherited ciliopathy characterized, among other dysfunctions, by renal defects for which the precise role of the cilia in kidney function remains unclear. We studied a cohort of patients with BBS where we found that these patients had a urinary concentration defect even when kidney function was near normal and in the absence of major cyst formation. Subsequent in vitro analysis showed that renal cells in which a BBS gene was knocked down were unciliated, but did not exhibit cell cycle defects. As the vasopressin receptor 2 is located in the primary cilium, we studied BBS-derived unciliated renal epithelial cells and found that they were unable to respond to luminal arginine vasopressin treatment and activate their luminal aquaporin 2. The ability to reabsorb water was restored by treating these unciliated renal epithelial cells with forskolin, a receptor-independent adenylate cyclase activator, showing that the intracellular machinery for water absorption was present but not activated. These findings suggest that the luminal receptor located on the primary cilium may be important for efficient transepithelial water absorption.

Bardet–Biedl syndrome

“…18 Urinary concentration defects are prevalent even in patients with near-normal renal function and no major cysts. 21 Speech deficit has been reported in 60% of patients. 22 This mainly consists of high-pitched nasal speech and children often do not develop intelligible speech before the age of four.…”

Diabetes Insipidus: A Review

“…Bardet-Biedl syndrome, another cause of NDI, is a rare autosomal recessive disorder with obesity, mental retardation, retinopathy, polydactyly, male hypogonadism as well as polydipsia and polyuria [101]. In this syndrome there is an absent ADH receptor not on the basolateral side of the cells, but rather on the luminal side [101].…”

“…Bardet-Biedl syndrome, another cause of NDI, is a rare autosomal recessive disorder with obesity, mental retardation, retinopathy, polydactyly, male hypogonadism as well as polydipsia and polyuria [101]. In this syndrome there is an absent ADH receptor not on the basolateral side of the cells, but rather on the luminal side [101]. Bartter syndrome, an AR disease, is also characterized by polyuria and polydipsia; however, the impaired urinary concentration and resulting polydipsia come from impaired Na + reabsorption in the TAL of Henle [102].…”

Anti‐fibrosis effect of BMP‐7 peptide functionalization on cobalt chromium alloy

“…The detached adherent fibroblasts were counted and analyzed by using a Scepter (Millipore) coultermethod-based automated cell counter. 28 Attached fibroblasts were designated as number of cells/cm 2 . Proliferation of the fibroblasts attached onto the substrates was determined via measuring the total quantity of trypsinized fibroblasts at 1, 3, and 7 days.…”