PMID- 37740796
OWN - NLM
STAT- MEDLINE
DCOM- 20230925
LR  - 20231011
IS  - 1420-9071 (Electronic)
IS  - 1420-682X (Linking)
VI  - 80
IP  - 10
DP  - 2023 Sep 23
TI  - FKBP5 deficiency attenuates calcium oxalate kidney stone formation by suppressing 
      cell-crystal adhesion, apoptosis and macrophage M1 polarization via inhibition of 
      NF-kappaB signaling.
PG  - 301
LID - 10.1007/s00018-023-04958-7 [doi]
AB  - Surgical crushing of stones alone has not addressed the increasing prevalence of 
      kidney stones. A promising strategy is to tackle the kidney damage and crystal 
      aggregation inherent in kidney stones with the appropriate therapeutic target. 
      FKBP prolyl isomerase 5 (FKBP5) is a potential predictor of kidney injury, but 
      its status in calcium oxalate (CaOx) kidney stones is not clear. This study 
      attempted to elucidate the role and mechanism of FKBP5 in CaOx kidney stones. 
      Lentivirus and adeno-associated virus were used to control FKBP5 expression in a 
      CaOx kidney stone model. Transcriptomic sequencing and immunological assays were 
      used to analyze the mechanism of FKBP5 deficiency in CaOx kidney stones. The 
      results showed that FKBP5 deficiency reduced renal tubular epithelial cells 
      (RTEC) apoptosis and promoted cell proliferation by downregulating BOK 
      expression. It also attenuated cell-crystal adhesion by downregulating the 
      expression of CDH4. In addition, it inhibited M1 polarization and chemotaxis of 
      macrophages by suppressing CXCL10 expression in RTEC. Moreover, the above 
      therapeutic effects were exerted by inhibiting the activation of NF-kappaB signaling. 
      Finally, in vivo experiments showed that FKBP5 deficiency attenuated stone 
      aggregation and kidney injury in mice. In conclusion, this study reveals that 
      FKBP5 deficiency attenuates cell-crystal adhesion, reduces apoptosis, promotes 
      cell proliferation, and inhibits macrophage M1 polarization and chemotaxis by 
      inhibiting NF-kappaB signaling. This provides a potential therapeutic target for CaOx 
      kidney stones.
CI  - (c) 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.
FAU - Song, Qianlin
AU  - Song Q
AD  - Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, 
      Wuhan, 430060, Hubei, People's Republic of China.
AD  - Central Laboratory, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 
      430060, Hubei, People's Republic of China.
FAU - Song, Chao
AU  - Song C
AD  - Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, 
      Wuhan, 430060, Hubei, People's Republic of China.
FAU - Chen, Xin
AU  - Chen X
AUID- ORCID: 0000-0003-3885-4944
AD  - Central Laboratory, Renmin Hospital of Wuhan University, Jiefang Road 238, Wuhan, 
      430060, Hubei, People's Republic of China. drxinchen@whu.edu.cn.
AD  - Reproductive Medical Center, Renmin Hospital of Wuhan University and Hubei Clinic 
      Research Center for Assisted Reproductive Technology and Embryonic Development, 
      Jiefang Road 238, Wuhan, 430060, Hubei, People's Republic of China. 
      drxinchen@whu.edu.cn.
FAU - Xiong, Yunhe
AU  - Xiong Y
AD  - Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, 
      Wuhan, 430060, Hubei, People's Republic of China.
FAU - Li, Lijun
AU  - Li L
AD  - School of Power and Mechanical Engineering, The Institute of Technological 
      Science, Wuhan University, South Donghu Road 8, Wuhan, 430072, Hubei, People's 
      Republic of China.
FAU - Liao, Wenbiao
AU  - Liao W
AD  - Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, 
      Wuhan, 430060, Hubei, People's Republic of China.
FAU - Xue, Longjian
AU  - Xue L
AD  - School of Power and Mechanical Engineering, The Institute of Technological 
      Science, Wuhan University, South Donghu Road 8, Wuhan, 430072, Hubei, People's 
      Republic of China. xuelongjian@whu.edu.cn.
FAU - Yang, Sixing
AU  - Yang S
AD  - Department of Urology, Renmin Hospital of Wuhan University, Jiefang Road 238, 
      Wuhan, 430060, Hubei, People's Republic of China. sxyang@whu.edu.cn.
LA  - eng
GR  - 82070723/National Natural Science Foundation of China/
GR  - 82270797/National Natural Science Foundation of China/
PT  - Journal Article
DEP - 20230923
PL  - Switzerland
TA  - Cell Mol Life Sci
JT  - Cellular and molecular life sciences : CMLS
JID - 9705402
RN  - 0 (NF-kappa B)
RN  - 2612HC57YE (Calcium Oxalate)
RN  - Nephrolithiasis, Calcium Oxalate
SB  - IM
MH  - Animals
MH  - Mice
MH  - *NF-kappa B
MH  - Calcium Oxalate
MH  - Signal Transduction
MH  - *Kidney Calculi/genetics
MH  - Apoptosis
OTO - NOTNLM
OT  - Cell-crystal adhesion
OT  - FKBP5
OT  - Immune regulation
OT  - Kidney stones
OT  - NF-kappaB signaling
EDAT- 2023/09/23 20:42
MHDA- 2023/09/25 06:42
CRDT- 2023/09/23 11:06
PHST- 2023/07/12 00:00 [received]
PHST- 2023/09/08 00:00 [accepted]
PHST- 2023/09/07 00:00 [revised]
PHST- 2023/09/25 06:42 [medline]
PHST- 2023/09/23 20:42 [pubmed]
PHST- 2023/09/23 11:06 [entrez]
AID - 10.1007/s00018-023-04958-7 [pii]
AID - 10.1007/s00018-023-04958-7 [doi]
PST - epublish
SO  - Cell Mol Life Sci. 2023 Sep 23;80(10):301. doi: 10.1007/s00018-023-04958-7.