Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice

Abstract Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking...

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Autores principales:	Marciana V. Sousa, Andressa G. Amaral, Jessica A. Freitas, Gilson M. Murata, Elieser H. Watanabe, Bruno E. Balbo, Marcelo D. Tavares, Renato A. Hortegal, Camila Rocon, Leandro E. Souza, Maria C. Irigoyen, Vera M. Salemi, Luiz F. Onuchic
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/46292682db654a409c0c5c0c4473acb6
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spelling	oai:doaj.org-article:46292682db654a409c0c5c0c4473acb62021-12-02T16:08:05ZSmoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice10.1038/s41598-021-93633-72045-2322https://doaj.org/article/46292682db654a409c0c5c0c4473acb62021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93633-7https://doaj.org/toc/2045-2322Abstract Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13–18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.Marciana V. SousaAndressa G. AmaralJessica A. FreitasGilson M. MurataElieser H. WatanabeBruno E. BalboMarcelo D. TavaresRenato A. HortegalCamila RoconLeandro E. SouzaMaria C. IrigoyenVera M. SalemiLuiz F. OnuchicNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marciana V. Sousa Andressa G. Amaral Jessica A. Freitas Gilson M. Murata Elieser H. Watanabe Bruno E. Balbo Marcelo D. Tavares Renato A. Hortegal Camila Rocon Leandro E. Souza Maria C. Irigoyen Vera M. Salemi Luiz F. Onuchic Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
description	Abstract Smoking has been associated with renal disease progression in ADPKD but the underlying deleterious mechanisms and whether it specifically worsens the cardiac phenotype remain unknown. To investigate these matters, Pkd1-deficient cystic mice and noncystic littermates were exposed to smoking from conception to 18 weeks of age and, along with nonexposed controls, were analyzed at 13–18 weeks. Renal cystic index and cyst-lining cell proliferation were higher in cystic mice exposed to smoking than nonexposed cystic animals. Smoking increased serum urea nitrogen in cystic and noncystic mice and independently enhanced tubular cell proliferation and apoptosis. Smoking also increased renal fibrosis, however this effect was much higher in cystic than in noncystic animals. Pkd1 deficiency and smoking showed independent and additive effects on reducing renal levels of glutathione. Systolic function and several cardiac structural parameters were also negatively affected by smoking and the Pkd1-deficient status, following independent and additive patterns. Smoking did not increase, however, cardiac apoptosis or fibrosis in cystic and noncystic mice. Notably, smoking promoted a much higher reduction in body weight in Pkd1-deficient than in noncystic animals. Our findings show that smoking aggravated the renal and cardiac phenotypes of Pkd1-deficient cystic mice, suggesting that similar effects may occur in human ADPKD.
format	article
author	Marciana V. Sousa Andressa G. Amaral Jessica A. Freitas Gilson M. Murata Elieser H. Watanabe Bruno E. Balbo Marcelo D. Tavares Renato A. Hortegal Camila Rocon Leandro E. Souza Maria C. Irigoyen Vera M. Salemi Luiz F. Onuchic
author_facet	Marciana V. Sousa Andressa G. Amaral Jessica A. Freitas Gilson M. Murata Elieser H. Watanabe Bruno E. Balbo Marcelo D. Tavares Renato A. Hortegal Camila Rocon Leandro E. Souza Maria C. Irigoyen Vera M. Salemi Luiz F. Onuchic
author_sort	Marciana V. Sousa
title	Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
title_short	Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
title_full	Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
title_fullStr	Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
title_full_unstemmed	Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice
title_sort	smoking accelerates renal cystic disease and worsens cardiac phenotype in pkd1-deficient mice
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/46292682db654a409c0c5c0c4473acb6
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Smoking accelerates renal cystic disease and worsens cardiac phenotype in Pkd1-deficient mice

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