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

Autor: Sousa MV; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Amaral AG; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Freitas JA; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Murata GM; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Watanabe EH; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Balbo BE; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil., Tavares MD; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Hortegal RA; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Rocon C; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Souza LE; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Irigoyen MC; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Salemi VM; Heart Institute, University of São Paulo School of Medicine, São Paulo, Brazil., Onuchic LF; Divisions of Nephrology and Molecular Medicine, Department of Medicine, University of São Paulo School of Medicine, Avenida Dr. Arnaldo, 455 - Sala 4304, São Paulo, SP, 01246-903, Brazil. lonuchic@usp.br.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2021 Jul 14; Vol. 11 (1), pp. 14443. Date of Electronic Publication: 2021 Jul 14.
DOI: 10.1038/s41598-021-93633-7
Abstrakt: 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.
(© 2021. The Author(s).)
Databáze: MEDLINE
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