Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

John J. Bissler; Fahad Zadjali; Dave Bridges; Aristotelis Astrinidis; Sharon Barone; Ying Yao; Je Anna R. Redd; Brian J. Siroky; Yanqing Wang; Joel T. Finley; Michael E. Rusiniak; Heinz Baumann; Kamyar Zahedi; Kenneth W. Gross; Manoocher Soleimani

doi:10.14814/phy2.13983

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

John J. Bissler^*, Fahad Zadjali, Dave Bridges, Aristotelis Astrinidis, Sharon Barone, Ying Yao, Je Anna R. Redd, Brian J. Siroky, Yanqing Wang, Joel T. Finley, Michael E. Rusiniak, Heinz Baumann, Kamyar Zahedi, Kenneth W. Gross, Manoocher Soleimani

^*Corresponding author for this work

Biochemistry

Research output: Contribution to journal › Article › peer-review

21 Citations (Scopus)

Abstract

Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

Original language	English
Article number	e13983
Journal	Physiological Reports
Volume	7
Issue number	2
DOIs	https://doi.org/10.14814/phy2.13983
Publication status	Published - Jan 2019

Keywords

Intercalated cells
Tuberous sclerosis complex
renal cystic disease
renal cystogenesis

ASJC Scopus subject areas

Physiology
Physiology (medical)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.14814/phy2.13983

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title = "Tuberous sclerosis complex exhibits a new renal cystogenic mechanism",

abstract = "Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.",

keywords = "Intercalated cells, Tuberous sclerosis complex, renal cystic disease, renal cystogenesis",

author = "Bissler, {John J.} and Fahad Zadjali and Dave Bridges and Aristotelis Astrinidis and Sharon Barone and Ying Yao and Redd, {Je Anna R.} and Siroky, {Brian J.} and Yanqing Wang and Finley, {Joel T.} and Rusiniak, {Michael E.} and Heinz Baumann and Kamyar Zahedi and Gross, {Kenneth W.} and Manoocher Soleimani",

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doi = "10.14814/phy2.13983",

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AU - Bissler, John J.

AU - Zadjali, Fahad

AU - Bridges, Dave

AU - Astrinidis, Aristotelis

AU - Barone, Sharon

AU - Yao, Ying

AU - Redd, Je Anna R.

AU - Siroky, Brian J.

AU - Wang, Yanqing

AU - Finley, Joel T.

AU - Rusiniak, Michael E.

AU - Baumann, Heinz

AU - Zahedi, Kamyar

AU - Gross, Kenneth W.

AU - Soleimani, Manoocher

PY - 2019/1

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N2 - Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

AB - Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc-mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

KW - Intercalated cells

KW - Tuberous sclerosis complex

KW - renal cystic disease

KW - renal cystogenesis

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Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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