Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease

Yuajit, Chaowalit; Muanprasat, Chatchai; Gallagher, Anna-Rachel; Fedeles, Sorin V.; Kittayaruksakul, Suticha; Homvisasevongsa, Sureeporn; Somlo, Stefan; Chatsudthipong, Varanuj

doi:10.1016/j.bcp.2014.01.038

Cited by 38 publications

(26 citation statements)

References 31 publications

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“…CFTR plays a central role in the ADPKD cyst inflation [48][49][50][51][52][53]. Early in the cystogenesis process, CFTR becomes abnormally activated in ADPKD cyst-lining cells [48][49][50][51][52][53]. Supporting the involvement of CFTR in ADPKD cyst inflation, it was shown that the fluid accumulation within cysts involves CFTR-like chloride currents [53] and it is slowed down either through inhibition or knockdown of CFTR [49][50][51][52][53].…”

Section: The Diseasementioning

confidence: 98%

“…The kidney cyst inflation with water and ions and continuous expansion throughout the patient life is assured by an abnormal transepithelial fluid secretion toward their lumen [47]. CFTR plays a central role in the ADPKD cyst inflation [48][49][50][51][52][53]. Early in the cystogenesis process, CFTR becomes abnormally activated in ADPKD cyst-lining cells [48][49][50][51][52][53].…”

Section: The Diseasementioning

confidence: 99%

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The Zebrafish Kupffer’s Vesicle: A Special Organ in a Model Organism to Study Human Diseases

Roxo-Rosa¹,

Lopes²

2020

Zebrafish in Biomedical Research

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The Kupffer's vesicle (KV) is a small, ciliated organ transiently present during embryogenesis of the zebrafish and other teleosts. The KV is required to the establishment of visceral laterality, such as the heart on the left side, being also known by the name left-right organizer (LRO). The LRO is found in other vertebrates, including mice, rabbits, frogs and human embryos. Among these, the KV became an excellent model organ to investigate the early left-right events during development and in disease. Many ciliary molecular players associated to the human disease primary ciliary dyskinesia have been tested in the zebrafish looking at KV cilia and its downstream effects on flow and left-right markers. Additionally, given its morphology and molecular features, we proposed the KV as a model organ to study the molecular mechanisms of the renal cyst inflation that occurs in the autosomal dominant polycystic kidney disease. Although having no connection to the kidney, the KV mimics a renal cyst because it is a fluid-filled vesicle, lined by monociliated epithelial cells that express polycystin-2, which knockdown leads to the organ luminal enlargement through changes in ion/water epithelial transport. Here, we explore the usefulness of the zebrafish KV to model these diseases. Keywords: Kupffer's vesicle (KV), left-right (LR), left-right organizer (LRO), primary ciliary dyskinesia (PCD), autosomal dominant polycystic kidney disease (ADPKD) Zebrafish in Biomedical Research

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Section: The Diseasementioning

confidence: 98%

Section: The Diseasementioning

confidence: 99%

The Zebrafish Kupffer’s Vesicle: A Special Organ in a Model Organism to Study Human Diseases

Roxo-Rosa¹,

Lopes²

2020

Zebrafish in Biomedical Research

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“…Proliferation is increased early in cyst formation in polycystic kidneys (22). We studied the role of AQP3 on cyst epithelial cell proliferation in vivo and in vitro .…”

Section: Resultsmentioning

confidence: 99%

Aquaporin‐3 deficiency slows cyst enlargement in experimental mouse models of autosomal dominant polycystic kidney disease

et al. 2019

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Human autosomal dominant polycystic kidney disease (ADPKD) is characterized by bilateral renal cysts that lead to a decline in kidney function. Previous studies reported aquaporin (AQP)‐3 expression in cysts derived from collecting ducts in ADPKD. To study the role of AQP3 in cyst development, we generated 2 polycystic kidney disease (PKD) mouse models: kidney‐specific Pkd1 knockout mice and inducible Pkd1 knockout mice, each without and with AQP3 deletion. In both models, kidney sizes and cyst indexes were significantly reduced in AQP3‐null PKD mice compared with AQP3‐expressing PKD mice, with the difference seen mainly in collecting duct cysts. AQP3‐deficient kidneys showed significantly reduced ATP content, increased phosphorylated (p)‐AMPK, and decreased p‐ERK and p‐mammalian target of rapamycin (mTOR). In a matrix‐grown Madin‐Darby canine kidney cyst model, AQP3 expression promoted cyst enlargement and was associated with increased expression of hypoxia‐inducible factor 1‐α and glucose transporter 1 and increased glucose uptake. Our data suggest that the slowed renal cyst enlargement in AQP3 deficiency involves impaired energy metabolism in the kidney through AMPK and mTOR signaling and impaired cellular glucose uptake. These findings implicate AQP3 as a novel determinant of renal cyst enlargement and hence a potential drug target in ADPKD.—Wang, W., Geng, X., Lei, L., Jia, Y., Li, Y., Zhou, H., Verkman, A. S., Yang, B. Aquaporin‐3 deficiency slows cyst enlargement in experimental mouse models of autosomal dominant polycystic kidney disease. FASEB J. 33, 6185–6196 (2019). http://www.fasebj.org

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“…Moreover, steviol allowed a decrease in kidney weight and size, cysts index and area, compared with the control group. Furthermore, also stevioside treatment promoted similar effects such as a reduced kidney weight and decreased cysts index, but unlike steviol, an improvement in serum blood urea nitrogen and creatinine was not observed [114]. Furthermore, steviol enhances the expression of lysosomal enzyme marker (LAMP2), indicating the lysosomal degradation of CFTR (playing an important role in fluid accumulation in cysts) and of B-catenin (important in cell proliferation pathway).…”

Section: Steviamentioning

confidence: 85%

Nutrients, Nutraceuticals and Xenobiotics Affecting Renal Health

Cosola

Sabatino

Bari

et al. 2018

Preprint

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Abstract:Chronic kidney disease (CKD) affects worldwide 8-16% of the population. In developed countries, the most important risk factors for CKD are diabetes, hypertension and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced nutrition and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and help to manage and curb the main risk factors for renal damage. While the concepts of protein and salt restriction in nephrology are historically acknowledged, the role of some nutrients on renal health and the importance of nutrition as a preventative measure for renal care are less known.In this review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals and xenobiotics on renal health and function. The effects on kidney of fibres, proteins, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol, both direct and indirect, in CKD and non-CKD condition, are reviewed here. In a view of a functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions and CKD are related to systemic dysfunctions such as chronic low-grade inflammation.

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Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease

Cited by 38 publications

References 31 publications

The Zebrafish Kupffer’s Vesicle: A Special Organ in a Model Organism to Study Human Diseases

The Zebrafish Kupffer’s Vesicle: A Special Organ in a Model Organism to Study Human Diseases

Aquaporin‐3 deficiency slows cyst enlargement in experimental mouse models of autosomal dominant polycystic kidney disease

Nutrients, Nutraceuticals and Xenobiotics Affecting Renal Health

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