PMID- 29788096
OWN - NLM
STAT- MEDLINE
DCOM- 20200218
LR  - 20200313
IS  - 1460-2385 (Electronic)
IS  - 0931-0509 (Linking)
VI  - 34
IP  - 2
DP  - 2019 Feb 1
TI  - pNaKtide ameliorates renal interstitial fibrosis through inhibition of 
      sodium-potassium adenosine triphosphatase-mediated signaling pathways in 
      unilateral ureteral obstruction mice.
PG  - 242-252
LID - 10.1093/ndt/gfy107 [doi]
AB  - BACKGROUND: Sodium-potassium adenosine triphosphatase (Na/K-ATPase) has been 
      shown to regulate Src activity by combining with Src to keep it in an inactive 
      form. We previously reported that Na/K-ATPase was downregulated in unilateral 
      ureteral obstruction (UUO) animals. In this study, we examined whether inhibition 
      of Na/K-ATPase-mediated Src signaling pathways ameliorated renal interstitial 
      fibrosis induced by UUO. METHODS: UUO was performed on male C57BL/6J mice. 
      pNaKtide, a mimic of Na/K-ATPase, was administered by intraperitoneal injection 
      on Day 0 and Day 4 after ureteral ligation. Markers of interstitial fibrosis, 
      inflammation and oxidative stress and transforming growth factor-beta1 (TGF-beta1) 
      expression were examined after the mice were sacrificed on Day 7. Activation of 
      Src and its downstream signaling effectors, including extracellular regulated 
      protein kinase 1/2 (ERK1/2), p38 mitogen-activated protein kinase (p38 MAPK) and 
      protein kinase B (AKT), were evaluated. RESULTS: pNaKtide administration markedly 
      attenuated myofibroblast accumulation and extracellular matrix deposition in 
      obstructed kidneys. Also, pNaKtide significantly reduced the increased expression 
      of 8-iso-prostaglandin F2alpha, TGF-beta1, interleukin-6 and monocyte chemoattractant 
      protein-1 (MCP-1), as well as reduced macrophage infiltration, in UUO animals. 
      All these changes were obtained, along with inhibition of Src and its downstream 
      effector activity. CONCLUSIONS: Na/K-ATPase-mediated signaling pathways 
      contribute to fibrogenesis and could represent a potential target in the 
      treatment of renal fibrosis.
FAU - Cheng, Xi
AU  - Cheng X
AD  - Renal Division, Department of Medicine, Peking University First Hospital.
AD  - Institute of Nephrology, Peking University.
AD  - Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of 
      Chronic Kidney Disease Prevention and Treatment, Ministry of Education.
FAU - Song, Yi
AU  - Song Y
AD  - Department of Urology, Peking University First Hospital, Beijing, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Renal Division, Department of Medicine, Peking University First Hospital.
AD  - Institute of Nephrology, Peking University.
AD  - Key Laboratory of Renal Disease, Ministry of Health of China, Key Laboratory of 
      Chronic Kidney Disease Prevention and Treatment, Ministry of Education.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Peptide Fragments)
RN  - 0 (Peptides)
RN  - 0 (Tgfb1 protein, mouse)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (pNaKtide)
RN  - 9NEZ333N27 (Sodium)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 7.2.2.13 (Sodium-Potassium-Exchanging ATPase)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Arteriosclerosis/pathology
MH  - Down-Regulation
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fibrosis/drug therapy
MH  - Kidney/pathology
MH  - Kidney Diseases/*drug therapy
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Oxidative Stress
MH  - Peptide Fragments/*pharmacology/therapeutic use
MH  - Peptides/*pharmacology/therapeutic use
MH  - Potassium/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - Sodium/metabolism
MH  - Sodium-Potassium-Exchanging ATPase/metabolism
MH  - Transforming Growth Factor beta1/metabolism
MH  - Ureteral Obstruction/*drug therapy/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
MH  - src-Family Kinases/metabolism
EDAT- 2018/05/23 06:00
MHDA- 2020/02/19 06:00
CRDT- 2018/05/23 06:00
PHST- 2017/12/20 00:00 [received]
PHST- 2018/03/17 00:00 [accepted]
PHST- 2018/05/23 06:00 [pubmed]
PHST- 2020/02/19 06:00 [medline]
PHST- 2018/05/23 06:00 [entrez]
AID - 4999269 [pii]
AID - 10.1093/ndt/gfy107 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2019 Feb 1;34(2):242-252. doi: 10.1093/ndt/gfy107.