scholarly journals Resident macrophages in cystic kidney disease

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0006052020
Author(s):  
Zhang Li ◽  
Kurt A. Zimmerman ◽  
Bradley K. Yoder
Keyword(s):  
Kidney Disease ◽  
Adult Mouse ◽  
Inflammatory Cell ◽  
Current Knowledge ◽  
Kidney Injury ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Pathological Conditions

Interstitial inflammation is an important feature of cystic kidney disease. Renal macrophages are the most well studied inflammatory cell in the kidney and their involvement in cyst formation has been reported in different animal models and patients with cystic kidney disease. Originally it was believed that renal macrophages were maintained from a constant supply of bone marrow-derived circulating monocytes and could be recruited to the kidney in response to local inflammation. However, this idea has been challenged using fate mapping methods by showing that at least two distinct developmental origins of macrophages are present in the adult mouse kidney. The first type, termed infiltrating macrophages, are recruited from circulating monocytes and gradually develop macrophage properties upon entering the kidney. The second type of macrophage, termed resident macrophages, predominantly originate from embryonic precursors, colonize the kidney during its development, and proliferate in situ to maintain their population throughout adulthood. Infiltrating and resident macrophages work together to maintain homeostasis and to properly respond to pathological conditions, such as acute kidney injury, cystic kidney disease, or infection. This review will briefly summarize current knowledge of resident macrophages in cystic kidney disease.

scholarly journals c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease

PLoS Genetics ◽  
2021 ◽  
Vol 17 (12) ◽  
pp. e1009711
Author(s):  
Abigail O. Smith ◽  
Julie A. Jonassen ◽  
Kenley M. Preval ◽  
Roger J. Davis ◽  
Gregory J. Pazour
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Diseases ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Nuclear Accumulation ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Jnk Pathway ◽  
Cystic Kidneys

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2. Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD.

scholarly journals Proximal Tubular Cysts in Fetal Human Autosomal Recessive Polycystic Kidney Disease

2000 ◽  
Vol 11 (4) ◽  
pp. 760-763 ◽  
Author(s):  
KOICHI NAKANISHI ◽  
WILLIAM E. SWEENEY ◽  
KLAUS ZERRES ◽  
LISA M. GUAY-WOODFORD ◽  
ELLIS D. AVNER
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Gestational Age ◽  
Autosomal Recessive ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Proximal Tubular ◽  
Collecting Tubules

Abstract. Standard texts describe human autosomal recessive polycystic kidney disease (ARPKD) as a cystic kidney disease in which lesions are localized to collecting tubules. Murine models of ARPKD consistently demonstrate an early phase of proximal tubular (PT) cystic involvement, which disappears shortly after birth. This is followed by a phase of collecting tubular (CT) cyst formation and progressive enlargement leading to compromise of renal function and death. Because the description of cystic lesions in human ARPKD has been largely based on postnatal specimens, PT cyst formation was hypothesized to be a characteristic feature of fetal human, as well as murine, ARPKD. This study examines nephron segment-specific cyst localization histochemically by lectin binding in 11 human ARPKD specimens obtained at different fetal and postnatal ages. PT cysts were found in human fetal specimens from gestational age 14 wk to 26 wk. The percentage of cysts involving PT segments ranged from 2 to 41%. The cystic index of PT cysts ranged from 2 to 5. In all specimens in which PT cysts were found, both the percentage of CT cysts and their cystic index were equal to or greater than the percentage of PT cysts and the associated PT cystic index. PT cysts were absent in all kidney specimens older than 34 wk gestational age. It is concluded that human ARPKD, like murine ARPKD, has a transient phase of PT cyst formation during early fetal development.

scholarly journals c-Jun N-terminal kinase (JNK) signaling contributes to cystic burden in polycystic kidney disease

2021 ◽  
Author(s):  
Abigail O Smith ◽  
Julie A Jonassen ◽  
Kenley M Preval ◽  
Roger J Davis ◽  
Gregory J. Pazour
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Kidney Diseases ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Nuclear Accumulation ◽  
Cystic Kidney ◽  
Polycystic Kidney ◽  
Jnk Pathway ◽  
Cystic Kidneys

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people. It primarily is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2). The most proximal effects of Pkd mutations leading to cyst formation are not known, but pro-proliferative signaling must be involved for the tubule epithelial cells to increase in number over time. The c-Jun N-terminal kinase (JNK) pathway promotes proliferation and is activated in acute and chronic kidney diseases. Using a mouse model of cystic kidney disease caused by Pkd2 loss, we observe JNK activation in cystic kidneys and observe increased nuclear phospho c-Jun in cystic epithelium. Genetic removal of Jnk1 and Jnk2 suppresses the nuclear accumulation of phospho c-Jun, reduces proliferation and reduces the severity of cystic disease. While Jnk1 and Jnk2 are thought to have largely overlapping functions, we find that Jnk1 loss is nearly as effective as the double loss of Jnk1 and Jnk2 . Jnk pathway inhibitors are in development for neurodegeneration, cancer, and fibrotic diseases. Our work suggests that the JNK pathway should be explored as a therapeutic target for ADPKD.

scholarly journals Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease

2008 ◽  
Vol 183 (3) ◽  
pp. 377-384 ◽  
Author(s):  
Julie A. Jonassen ◽  
Jovenal San Agustin ◽  
John A. Follit ◽  
Gregory J. Pazour
Keyword(s):  
Kidney Disease ◽  
Primary Cilia ◽  
Collecting Duct ◽  
Cyst Formation ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Duct Cells ◽  
Cell Proliferation And Differentiation ◽  
Cilia Formation ◽  
Collecting Duct Cells

Primary cilia project from the surface of most vertebrate cells and are thought to be sensory organelles. Defects in primary cilia lead to cystic kidney disease, although the ciliary mechanisms that promote and maintain normal renal function remain incompletely understood. In this work, we generated a floxed allele of the ciliary assembly gene Ift20. Deleting this gene specifically in kidney collecting duct cells prevents cilia formation and promotes rapid postnatal cystic expansion of the kidney. Dividing collecting duct cells in early stages of cyst formation fail to properly orient their mitotic spindles along the tubule, whereas nondividing cells improperly position their centrosomes. At later stages, cells lacking cilia have increased canonical Wnt signaling and increased rates of proliferation. Thus, IFT20 functions to couple extracellular events to cell proliferation and differentiation.

Phthalate Esters, Cystic Kidney Disease in Animals and Possible Effects on Human Health: A Review

1990 ◽  
Vol 9 (6) ◽  
pp. 397-401 ◽  
Author(s):  
K.N. Woodward
Keyword(s):  
Kidney Disease ◽  
Human Health ◽  
Phthalate Esters ◽  
Renal Cysts ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Peroxisome Proliferation ◽  
Peroxisome Proliferators ◽  
Prolonged Administration ◽  
Route Of Exposure

1 Phthalate esters are known to cause hepatic peroxisome proliferation in rodents and, after prolonged administration, hepatocarcinogenesis. Peroxisome proliferators as a group are hepatocarcinogenic. The mechanism is not known but it does not appear to involve a direct genotoxic element. 2 DEHP and DBP have been shown to cause renal cysts in rodents and they also produce renal peroxisome proliferation. There are no data to causally link the two phenomena. 3 Although renal cysts have been noted in haemodialysis patients and haemodialysis is a route of exposure to DEHP, there are no data to suggest a cause and effect relationship. 4 More studies are needed on the mechanism of renal cystogenesis.

Robinow syndrome: report of two patients with cystic kidney disease

2008 ◽  
Vol 37 (6) ◽  
pp. 481-484 ◽  
Author(s):  
Lynn Wiens ◽  
D. K. Strickland ◽  
Barbara Sniffen ◽  
Bradley A. Warady
Keyword(s):  
Kidney Disease ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Robinow Syndrome ◽  
Syndrome Report

scholarly journals New PAX2 Mutation Associated with Polycystic Kidney Disease: A Case Report

2021 ◽  
Vol 15 ◽  
pp. 117955652199235
Author(s):  
Jessica Maria Forero-Delgadillo ◽  
Vanessa Ochoa ◽  
Natalia Duque ◽  
Jaime Manuel Restrepo ◽  
Hernando Londoño ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Novel Mutation ◽  
Clinical Manifestations ◽  
Renal Cysts ◽  
Renal Dysplasia ◽  
Cystic Kidney Disease ◽  
Cystic Kidney ◽  
Incomplete Penetrance ◽  
Wide Range ◽  
Stage Renal Disease

Background: Congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage renal disease in children. Diagnosis by genetic testing has proven challenging due to its genetic and phenotypic heterogeneity, as well as incomplete penetrance. We report a case on a 16-months old female with a history of renal cysts and a PAX2 mutation. Case presentation: The patient presented with a prenatal diagnosis of Potter sequence and a postnatal diagnosis of renal cysts. An ultrasound at 20 weeks gestation revealed right renal agenesis and possible left renal dysplasia. Post natal genetic analyses identified a novel mutation in PAX2. Conclusion: Cystic kidney disease is often underdiagnosed due to its variable expressivity and wide range of clinical manifestations; PAX2 genetic screening should be considered for all patients with CAKUT.

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