PMID- 28341273
OWN - NLM
STAT- MEDLINE
DCOM- 20180417
LR  - 20211204
IS  - 1523-1755 (Electronic)
IS  - 0085-2538 (Linking)
VI  - 92
IP  - 2
DP  - 2017 Aug
TI  - Branched-chain amino acids enhance cyst development in autosomal dominant 
      polycystic kidney disease.
PG  - 377-387
LID - S0085-2538(17)30072-8 [pii]
LID - 10.1016/j.kint.2017.01.021 [doi]
AB  - Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the 
      progressive development of kidney and liver cysts. The mammalian target of 
      rapamycin (mTOR) cascade is one of the important pathways regulating cyst growth 
      in ADPKD. Branched-chain amino acids (BCAAs), including leucine, play a crucial 
      role to activate mTOR pathway. Therefore, we administered BCAA dissolved in the 
      drinking water to Pkd1(flox/flox):Mx1-Cre (cystic) mice from four to 22 weeks of 
      age after polyinosinic-polycytidylic acid-induced conditional Pkd1 knockout at 
      two weeks of age. The BCAA group showed significantly greater kidney/body weight 
      ratio and higher cystic index in both the kidney and liver compared to the 
      placebo-treated mice. We found that the L-type amino acid transporter 1 that 
      facilitates BCAA entry into cells is strongly expressed in cells lining the 
      cysts. We also found increased cyst-lining cell proliferation and upregulation of 
      mTOR and mitogen-activated protein kinase/extracellular signal-regulated kinase 
      (MAPK/ERK) pathways in the BCAA group. In vitro, we cultured renal epithelial 
      cell lines from Pkd1 null mice with or without leucine. Leucine was found to 
      stimulate cell proliferation, as well as activate mTOR and MAPK/ERK pathways in 
      these cells. Thus, BCAA accelerated disease progression by mTOR and MAPK/ERK 
      pathways. Hence, BCAA may be harmful to patients with ADPKD.
CI  - Copyright (c) 2017 International Society of Nephrology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Yamamoto, Junya
AU  - Yamamoto J
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Nishio, Saori
AU  - Nishio S
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan. Electronic address: 
      saorin@med.hokudai.ac.jp.
FAU - Hattanda, Fumihiko
AU  - Hattanda F
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Nakazawa, Daigo
AU  - Nakazawa D
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Kimura, Toru
AU  - Kimura T
AD  - Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 
      Tokyo, Japan.
FAU - Sata, Michio
AU  - Sata M
AD  - Liver Cancer Research Division, Kurume University, Kurume, Japan.
FAU - Makita, Minoru
AU  - Makita M
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Ishikawa, Yasunobu
AU  - Ishikawa Y
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
FAU - Atsumi, Tatsuya
AU  - Atsumi T
AD  - Division of Rheumatology, Endocrinology and Nephrology, Hokkaido University 
      Graduate School of Medicine, Sapporo, Japan.
LA  - eng
PT  - Journal Article
DEP - 20170322
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Amino Acids, Branched-Chain)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acids, Branched-Chain/*toxicity
MH  - Animals
MH  - *Disease Models, Animal
MH  - *MAP Kinase Signaling System
MH  - Mice
MH  - Polycystic Kidney, Autosomal Dominant/*chemically induced/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/*metabolism
OTO - NOTNLM
OT  - ADPKD
OT  - BCAA
OT  - LAT-1
OT  - mTOR
EDAT- 2017/03/28 06:00
MHDA- 2018/04/18 06:00
CRDT- 2017/03/26 06:00
PHST- 2016/04/27 00:00 [received]
PHST- 2017/01/03 00:00 [revised]
PHST- 2017/01/05 00:00 [accepted]
PHST- 2017/03/28 06:00 [pubmed]
PHST- 2018/04/18 06:00 [medline]
PHST- 2017/03/26 06:00 [entrez]
AID - S0085-2538(17)30072-8 [pii]
AID - 10.1016/j.kint.2017.01.021 [doi]
PST - ppublish
SO  - Kidney Int. 2017 Aug;92(2):377-387. doi: 10.1016/j.kint.2017.01.021. Epub 2017 
      Mar 22.