PMID- 25349217
OWN - NLM
STAT- MEDLINE
DCOM- 20150922
LR  - 20220410
IS  - 1535-3699 (Electronic)
IS  - 1535-3702 (Print)
IS  - 1535-3699 (Linking)
VI  - 240
IP  - 7
DP  - 2015 Jul
TI  - Rapamycin ameliorates IgA nephropathy via cell cycle-dependent mechanisms.
PG  - 936-45
LID - 10.1177/1535370214555666 [doi]
AB  - IgA nephropathy is the most frequent type of glomerulonephritis worldwide. The 
      role of cell cycle regulation in the pathogenesis of IgA nephropathy has been 
      studied. The present study was designed to explore whether rapamycin ameliorates 
      IgA nephropathy via cell cycle-dependent mechanisms. After establishing an IgA 
      nephropathy model, rats were randomly divided into four groups. Coomassie 
      Brilliant Blue was used to measure the 24-h urinary protein levels. Renal 
      function was determined using an autoanalyzer. Proliferation was assayed via 
      Proliferating Cell Nuclear Antigen (PCNA) immunohistochemistry. Rat mesangial 
      cells were cultured and divided into the six groups. 
      Methylthiazolyldiphenyl-tetrazolium bromide (MTT) and flow cytometry were used to 
      detect cell proliferation and the cell cycle phase. Western blotting was 
      performed to determine cyclin E, cyclin-dependent kinase 2, p27(Kip1), 
      p70S6K/p-p70S6K, and extracellular signal-regulated kinase 1/2/p- extracellular 
      signal-regulated kinase 1/2 protein expression. A low dose of the mammalian 
      target of rapamycin (mTOR) inhibitor rapamycin prevented an additional increase 
      in proteinuria, protected kidney function, and reduced IgA deposition in a model 
      of IgA nephropathy. Rapamycin inhibited mesangial cell proliferation and arrested 
      the cell cycle in the G1 phase. Rapamycin did not affect the expression of cyclin 
      E and cyclin-dependent kinase 2. However, rapamycin upregulated p27(Kip1) at 
      least in part via AKT (also known as protein kinase B)/mTOR. In conclusion, 
      rapamycin can affect cell cycle regulation to inhibit mesangial cell 
      proliferation, thereby reduce IgA deposition, and slow the progression of IgAN.
CI  - (c) 2014 by the Society for Experimental Biology and Medicine.
FAU - Tian, Jihua
AU  - Tian J
AD  - Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical 
      University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, 
      Taiyuan, Shanxi, 030012, China Department of Microbiology and Immunology, Shanxi 
      Medical University, Taiyuan, Shanxi, 030001, China.
FAU - Wang, Yanhong
AU  - Wang Y
AD  - Department of Microbiology and Immunology, Shanxi Medical University, Taiyuan, 
      Shanxi, 030001, China.
FAU - Liu, Xinyan
AU  - Liu X
AD  - Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical 
      University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, 
      Taiyuan, Shanxi, 030012, China.
FAU - Zhou, Xiaoshuang
AU  - Zhou X
AD  - Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical 
      University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, 
      Taiyuan, Shanxi, 030012, China.
FAU - Li, Rongshan
AU  - Li R
AD  - Department of Nephrology, The Affiliated People's Hospital of Shanxi Medical 
      University, Shanxi Provincial People's Hospital, Shanxi Kidney Disease Institute, 
      Taiyuan, Shanxi, 030012, China rongshanli13@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141027
PL  - Switzerland
TA  - Exp Biol Med (Maywood)
JT  - Experimental biology and medicine (Maywood, N.J.)
JID - 100973463
RN  - 0 (Immunosuppressive Agents)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Cycle/*drug effects
MH  - Cell Proliferation/drug effects
MH  - Disease Models, Animal
MH  - Flow Cytometry
MH  - Fluorescent Antibody Technique
MH  - Glomerulonephritis, IGA/*pathology
MH  - Immunohistochemistry
MH  - Immunosuppressive Agents/*pharmacology
MH  - Male
MH  - Mesangial Cells/*drug effects
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sirolimus/*pharmacology
PMC - PMC4935411
OTO - NOTNLM
OT  - IgA nephropathy
OT  - Rapamycin
OT  - cell cycle proteins
OT  - mesangial cell
EDAT- 2014/10/29 06:00
MHDA- 2015/09/24 06:00
PMCR- 2016/01/01
CRDT- 2014/10/29 06:00
PHST- 2014/07/11 00:00 [received]
PHST- 2014/09/07 00:00 [accepted]
PHST- 2014/10/29 06:00 [entrez]
PHST- 2014/10/29 06:00 [pubmed]
PHST- 2015/09/24 06:00 [medline]
PHST- 2016/01/01 00:00 [pmc-release]
AID - 1535370214555666 [pii]
AID - 10.1177_1535370214555666 [pii]
AID - 10.1177/1535370214555666 [doi]
PST - ppublish
SO  - Exp Biol Med (Maywood). 2015 Jul;240(7):936-45. doi: 10.1177/1535370214555666. 
      Epub 2014 Oct 27.