Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Di Liu; Yexin Liu; Guochun Chen; Liyu He; Chengyuan Tang; Chang Wang; Danyi Yang; Huiqiong Li; Zheng Dong; Hong Liu

doi:10.1159/000456039

Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

Di Liu, Yexin Liu, Guochun Chen, Liyu He, Chengyuan Tang, Chang Wang, Danyi Yang, Huiqiong Li, Zheng Dong, Hong Liu

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

26 Scopus citations

Abstract

Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: Control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

Original language	English (US)
Pages (from-to)	293-300
Number of pages	8
Journal	American Journal of Nephrology
Volume	45
Issue number	4
DOIs	https://doi.org/10.1159/000456039
State	Published - Apr 1 2017
Externally published	Yes

Keywords

Autophagy
Cell cycle
Cell proliferation
IgA nephropathy
Mamalian target of rapamycin
Rapamycin

ASJC Scopus subject areas

Nephrology

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10.1159/000456039

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title = "Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy",

abstract = "Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: Control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.",

keywords = "Autophagy, Cell cycle, Cell proliferation, IgA nephropathy, Mamalian target of rapamycin, Rapamycin",

author = "Di Liu and Yexin Liu and Guochun Chen and Liyu He and Chengyuan Tang and Chang Wang and Danyi Yang and Huiqiong Li and Zheng Dong and Hong Liu",

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doi = "10.1159/000456039",

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T1 - Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

AU - Liu, Di

AU - Liu, Yexin

AU - Chen, Guochun

AU - He, Liyu

AU - Tang, Chengyuan

AU - Wang, Chang

AU - Yang, Danyi

AU - Li, Huiqiong

AU - Dong, Zheng

AU - Liu, Hong

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: Control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

AB - Background: IgA nephropathy (IgAN) has been considered to be the most frequent form of primary glomerulonephritis that occurs worldwide with a variety of factors involved in its occurrence and development. The impact of autophagy in IgAN, however, remains partially unclear. This study was designed to investigate the effects of rapamycin in an IgAN model. Method: After establishing an IgAN rat model, SD rats were divided into 4 groups: Control, control + rapamycin, IgAN, IgAN + rapamycin. Proteinuria and the pathological changes and the level of autophagy of kidney were texted. Identify the expression of phosphorylation and total mammalian target of rapamycin (mTOR) and s6k1 as well as cyclin D1 in the kidney of rats through Western blot and immunohistochemistry. Results: With rapamycin treatment, we observed a significant reduction in the progression of proteinuria as well as alleviation of pathological lesions in IgAN rats. Besides, autophagy was inhibited, while the mTOR/S6k1 pathway was activated and expression of cyclin D1 was increased in IgAN. Rapamycin treatment increased autophagy and decreased the expression of cyclin D1. Conclusion: These results may suggest that mTOR-mediated autophagy inhibition may result in mesangial cell proliferation in IgAN.

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KW - Cell cycle

KW - Cell proliferation

KW - IgA nephropathy

KW - Mamalian target of rapamycin

KW - Rapamycin

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Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy

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