PMID- 38167222
OWN - NLM
STAT- MEDLINE
DCOM- 20240207
LR  - 20240424
IS  - 1423-0143 (Electronic)
IS  - 1420-4096 (Linking)
VI  - 49
IP  - 1
DP  - 2024
TI  - Inflammation Is More Sensitive than Cell Proliferation in Response to Rapamycin 
      Treatment in Polycystic Kidney Disease.
PG  - 60-68
LID - 10.1159/000535750 [doi]
AB  - INTRODUCTION: It has been reported that rapamycin inhibited inflammation in renal 
      interstitial diseases. We therefore hypothesized that rapamycin could attenuate 
      inflammation in polycystic kidney disease (PKD). METHODS: Han:SPRD rats were 
      treated with rapamycin by daily gavage from 4 weeks to 12 weeks of age at the 
      dosage of 0.5 mg/kg/day (low dose) or 1 mg/kg/day (high dose). WT9-12 human PKD 
      cells were treated with various concentrations of rapamycin. RESULTS: 
      Two-kidney/total body weight ratio and cystic index in Cy/+ kidneys were 
      significantly reduced with the treatment of low-dose rapamycin and further 
      reduced by the treatment with high-dose rapamycin. However, the renal function of 
      Cy/+ rats was equally improved by the treatment with either low-dose or high-dose 
      rapamycin. The renal cell proliferation was significantly decreased in Cy/+ 
      kidneys with the treatment of low-dose rapamycin and was further decreased with 
      the treatment of high-dose rapamycin as examined by Ki67 staining. The 
      phosphorylation of S6K in cystic kidneys was decreased by low-dose rapamycin and 
      further decreased by high-dose rapamycin. Both low-dose and high-dose rapamycin 
      treatment decreased macrophage infiltration and the expression of complement 
      factor B (CFB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis 
      factor-alpha (TNF-alpha) to a similar level. The expression of CFB, MCP-1, and TNF-alpha 
      and phosphorylation of S6K were inhibited in WT9-12 cells treated with 10 
      n<sc>m</sc> rapamycin at 24 h and 48 h, respectively. Moreover, the 
      phosphorylation of Akt was not increased by 1 n<sc>m</sc> and 10 n<sc>m</sc> of 
      rapamycin and enhanced by 1 mu<sc>m</sc> rapamycin treatment. Interestingly, 
      WT9-12 cell proliferation could be inhibited by 1 mu<sc>m</sc> rapamycin. 
      CONCLUSION: Low dose of rapamycin could inhibit inflammation and protect renal 
      function in PKD. Inflammation is more sensitive than cell proliferation in 
      response to rapamycin treatment in PKD.
CI  - (c) 2024 The Author(s). Published by S. Karger AG, Basel.
FAU - Yang, Ming
AU  - Yang M
AD  - Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, China.
FAU - Lv, Jiayi
AU  - Lv J
AD  - Department of Nephrology, Shanghai Changzheng Hospital, Second Affiliated 
      Hospital of Naval Medical University (Second Military Medical University), 
      Shanghai, China.
FAU - Gong, Chanjuan
AU  - Gong C
AD  - Department of Nephrology, Shanghai Changzheng Hospital, Second Affiliated 
      Hospital of Naval Medical University (Second Military Medical University), 
      Shanghai, China.
FAU - Xue, Cheng
AU  - Xue C
AD  - Department of Nephrology, Shanghai Changzheng Hospital, Second Affiliated 
      Hospital of Naval Medical University (Second Military Medical University), 
      Shanghai, China, chengxia1568@126.com.
FAU - Fu, Lili
AU  - Fu L
AD  - Department of Nephrology, Shanghai Changzheng Hospital, Second Affiliated 
      Hospital of Naval Medical University (Second Military Medical University), 
      Shanghai, China.
FAU - Chen, Shunjie
AU  - Chen S
AD  - Department of Nephrology, Shanghai Fourth People's Hospital, School of Medicine, 
      Tongji University, Shanghai, China.
FAU - Mei, Changlin
AU  - Mei C
AD  - Department of Nephrology, Shanghai Changzheng Hospital, Second Affiliated 
      Hospital of Naval Medical University (Second Military Medical University), 
      Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20240102
PL  - Switzerland
TA  - Kidney Blood Press Res
JT  - Kidney & blood pressure research
JID - 9610505
RN  - W36ZG6FT64 (Sirolimus)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Rats
MH  - Humans
MH  - Animals
MH  - Sirolimus/pharmacology/therapeutic use
MH  - *Polycystic Kidney, Autosomal Dominant/drug therapy/metabolism
MH  - Tumor Necrosis Factor-alpha
MH  - *Polycystic Kidney Diseases/pathology
MH  - Kidney/pathology
MH  - Inflammation/pathology
MH  - Cell Proliferation
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - Cell proliferation
OT  - Inflammation
OT  - Polycystic kidney disease
OT  - Rapamycin
EDAT- 2024/01/04 01:18
MHDA- 2024/02/07 06:43
CRDT- 2024/01/03 09:38
PHST- 2023/07/04 00:00 [received]
PHST- 2023/12/02 00:00 [accepted]
PHST- 2024/02/07 06:43 [medline]
PHST- 2024/01/04 01:18 [pubmed]
PHST- 2024/01/03 09:38 [entrez]
AID - 000535750 [pii]
AID - 10.1159/000535750 [doi]
PST - ppublish
SO  - Kidney Blood Press Res. 2024;49(1):60-68. doi: 10.1159/000535750. Epub 2024 Jan 
      2.