scholarly journals Mutations in INVS encoding inversin cause nephronophthisis type 2, linking renal cystic disease to the function of primary cilia and left-right axis determination

2003 ◽  
Vol 34 (4) ◽  
pp. 413-420 ◽  
Author(s):  
Edgar A Otto ◽  
Bernhard Schermer ◽  
Tomoko Obara ◽  
John F O'Toole ◽  
Karl S Hiller ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Cystic Disease ◽  
Renal Cystic Disease

scholarly journals Tissue-Resident Macrophages Promote Renal Cystic Disease

2019 ◽  
Vol 30 (10) ◽  
pp. 1841-1856 ◽  
Author(s):  
Kurt A. Zimmerman ◽  
Cheng J. Song ◽  
Zhang Li ◽  
Jeremie M. Lever ◽  
David K. Crossman ◽  
...  
Keyword(s):  
Renal Injury ◽  
Primary Cilia ◽  
Kinase Inhibitor ◽  
Renal Cyst ◽  
Cyst Formation ◽  
Mutant Mice ◽  
Cystic Disease ◽  
Renal Cystic Disease ◽  
Resident Macrophage ◽  
Membrane Bound

BackgroundMutations affecting cilia proteins have an established role in renal cyst formation. In mice, the rate of cystogenesis is influenced by the age at which cilia dysfunction occurs and whether the kidney has been injured. Disruption of cilia function before postnatal day 12–14 results in rapid cyst formation; however, cyst formation is slower when cilia dysfunction is induced after postnatal day 14. Rapid cyst formation can also be induced in conditional adult cilia mutant mice by introducing renal injury. Previous studies indicate that macrophages are involved in cyst formation, however the specific role and type of macrophages responsible has not been clarified.MethodsWe analyzed resident macrophage number and subtypes during postnatal renal maturation and after renal injury in control and conditional Ift88 cilia mutant mice. We also used a pharmacological inhibitor of resident macrophage proliferation and accumulation to determine the importance of these cells during rapid cyst formation.ResultsOur data show that renal resident macrophages undergo a phenotypic switch from R2b (CD11clo) to R2a (CD11chi) during postnatal renal maturation. The timing of this switch correlates with the period in which cyst formation transitions from rapid to slow following induction of cilia dysfunction. Renal injury induces the reaccumulation of juvenile-like R2b resident macrophages in cilia mutant mice and restores rapid cystogenesis. Loss of primary cilia in injured conditional Ift88 mice results in enhanced epithelial production of membrane-bound CSF1, a cytokine that promotes resident macrophage proliferation. Inhibiting CSF1/CSF1-receptor signaling with a CSF1R kinase inhibitor reduces resident macrophage proliferation, R2b resident macrophage accumulation, and renal cyst formation in two mouse models of cystic disease.ConclusionsThese data uncover an important pathogenic role for resident macrophages during rapid cyst progression.

Oral-facial-digital type 1 syndrome

2018 ◽  
Author(s):  
Brunella Franco
Keyword(s):  
Oral Cavity ◽  
Primary Cilia ◽  
Phenotypic Variability ◽  
Clinical Spectrum ◽  
Dominant Male ◽  
Cystic Disease ◽  
Renal Cystic Disease ◽  
The Face ◽  
High Degree

This chapter discusses oral-facial-digital type 1 syndrome (OFD1), which represents a rare syndromic form of inherited renal cystic disease associated with dysfunction of primary cilia. The disease is transmitted as an X-linked dominant male lethal trait. Embryonic lethality in affected hemizygous males is usually reported in the first and second trimesters of pregnancy. The clinical spectrum for this disease includes malformation of the face, oral cavity, and digits with a high degree of phenotypic variability, even within the same family, possibly due to X-inactivation. Renal cystic disease is present in over 65% of adult cases and is usually observed in the second and third decades of life.

scholarly journals Autosomal recessive polycystic kidney disease and complex nephronophtisis medullary cystic disease

2008 ◽  
Vol 136 (Suppl. 4) ◽  
pp. 348-352
Author(s):  
Emilija Golubovic
Keyword(s):  
Kidney Disease ◽  
Mammalian Cells ◽  
Autosomal Recessive ◽  
Primary Cilia ◽  
Calcium Influx ◽  
Control Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Cystic Disease ◽  
Renal Cystic Disease

Reseach during the past decade has led to the discovery that defects in some proteins that localize to primary cilia or the basal body are the main contributors to renal cyst development. Autosomal recessive polycystic disease and nephronophthisis-medullary cystic kidney disease are named ciliopathies. The cilium is a microtubule-based organelle that is found on most mammalian cells. Cilia-mediated hypothesis has evolved into the concept of cystogenesis, cilia bend by fluid initiate a calcium influx that prevents cyst formation. Cilia might sense stimuli in the cell enviroment and control cell polarity and mitosis. A new set of pathogenic mechanisms in renal cystic disease defined new therapeutic targets, control of intracellular calcium, inhibition of cAMP and down regulation cannonical Wnt signaling.

Renal cystic disease

1999 ◽  
Vol 11 (2) ◽  
pp. 141-151 ◽  
Author(s):  
Friedhelm Hildebrandt
Keyword(s):  
Cystic Disease ◽  
Renal Cystic Disease

Polaris, a protein disrupted inorpkmutant mice, is required for assembly of renal cilium

2002 ◽  
Vol 282 (3) ◽  
pp. F541-F552 ◽  
Author(s):  
Bradley K. Yoder ◽  
Albert Tousson ◽  
Leigh Millican ◽  
John H. Wu ◽  
Charles E. Bugg ◽  
...  
Keyword(s):  
Primary Cilia ◽  
Collecting Duct ◽  
Physiological Role ◽  
Duct Cell ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Apical Surface ◽  
Cystic Disease ◽  
Cortical Collecting Duct

Cilia are organelles that play diverse roles, from fluid movement to sensory reception. Polaris, a protein associated with cystic kidney disease in Tg737°rpkmice, functions in a ciliogenic pathway. Here, we explore the role of polaris in primary cilia on Madin-Darby canine kidney cells. The results indicate that polaris localization and solubility change dramatically during cilia formation. These changes correlate with the formation of basal bodies and large protein rafts at the apical surface of the epithelia. A cortical collecting duct cell line has been derived from mice with a mutation in the Tg737 gene. These cells do not develop normal cilia, which can be corrected by reexpression of the wild-type Tg737 gene. These data suggest that the primary cilia are important for normal renal function and/or development and that the ciliary defect may be a contributing factor to the cystic disease in Tg737°rpkmice. Further characterization of these cells will be important in elucidating the physiological role of renal cilia and in determining their relationship to cystic disease.

AMR Series Unilateral (Localized) Renal Cystic Disease

2005 ◽  
Vol 12 (4) ◽  
pp. 227-232 ◽  
Author(s):  
Michele Bisceglia ◽  
Giuseppe Cret??
Keyword(s):  
Cystic Disease ◽  
Renal Cystic Disease
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