PMID- 28237991 OWN - NLM STAT- MEDLINE DCOM- 20180116 LR - 20211204 IS - 1421-9670 (Electronic) IS - 0250-8095 (Linking) VI - 45 IP - 4 DP - 2017 TI - Rapamycin Enhances Repressed Autophagy and Attenuates Aggressive Progression in a Rat Model of IgA Nephropathy. PG - 293-300 LID - 10.1159/000456039 [doi] 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. CI - (c) 2017 S. Karger AG, Basel. FAU - Liu, Di AU - Liu D AD - Nephrology Department, 2nd Xiangya Hospital, Central South University, Blood Purification Center in 2nd Xiangya Hospital of Central South University, Key Laboratory of Kidney Disease and Blood Purification in Hunan, Changsha, PR China. FAU - Liu, Yexin AU - Liu Y FAU - Chen, Guochun AU - Chen G FAU - He, Liyu AU - He L FAU - Tang, Chengyuan AU - Tang C FAU - Wang, Chang AU - Wang C FAU - Yang, Danyi AU - Yang D FAU - Li, Huiqiong AU - Li H FAU - Dong, Zheng AU - Dong Z FAU - Liu, Hong AU - Liu H LA - eng PT - Journal Article DEP - 20170225 PL - Switzerland TA - Am J Nephrol JT - American journal of nephrology JID - 8109361 RN - 0 (Ccnd1 protein, rat) RN - 0 (Immunosuppressive Agents) RN - 136601-57-5 (Cyclin D1) RN - EC 2.7.1.1 (mTOR protein, rat) RN - EC 2.7.11.1 (Ribosomal Protein S6 Kinases) RN - EC 2.7.11.1 (Rps6kb1 protein, rat) RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - W36ZG6FT64 (Sirolimus) SB - IM MH - Animals MH - Autophagy/*drug effects MH - Cell Proliferation/drug effects MH - Cyclin D1/metabolism MH - Disease Models, Animal MH - Glomerulonephritis, IGA/*drug therapy/pathology/urine MH - Humans MH - Immunohistochemistry MH - Immunosuppressive Agents/*therapeutic use MH - Mesangial Cells/drug effects/*pathology/ultrastructure MH - Microscopy, Electron MH - Proteinuria/drug therapy/urine MH - Rats MH - Rats, Sprague-Dawley MH - Ribosomal Protein S6 Kinases/metabolism MH - Signal Transduction/*drug effects MH - Sirolimus/*therapeutic use MH - TOR Serine-Threonine Kinases/metabolism EDAT- 2017/02/27 06:00 MHDA- 2018/01/18 06:00 CRDT- 2017/02/27 06:00 PHST- 2016/10/17 00:00 [received] PHST- 2017/01/08 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2018/01/18 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] AID - 000456039 [pii] AID - 10.1159/000456039 [doi] PST - ppublish SO - Am J Nephrol. 2017;45(4):293-300. doi: 10.1159/000456039. Epub 2017 Feb 25.