PMID- 31116709
OWN - NLM
STAT- MEDLINE
DCOM- 20191206
LR  - 20211204
IS  - 1643-3750 (Electronic)
IS  - 1234-1010 (Print)
IS  - 1234-1010 (Linking)
VI  - 25
DP  - 2019 May 22
TI  - Klotho Protein Reduced the Expression of Matrix Metalloproteinase-1 (MMP-1) and 
      Matrix Metalloproteinase-3 (MMP-3) in Fibroblasts from Patients with Pelvic Organ 
      Prolapse (POP) by Down-Regulating the Phosphorylation of ERK1/2.
PG  - 3815-3824
LID - 10.12659/MSM.913623 [doi]
AB  - BACKGROUND Pelvic organ prolapse (POP) is due to age-related atrophy and the 
      weakening of the tissues of the pelvic floor, with degradation of collagen and 
      extracellular matrix (ECM) by metalloproteinases (MMPs). This study aimed to 
      investigates the role of the age-related enzyme klotho, encoded by the KL gene, 
      in cultured fibroblasts obtained from patients with POP and the levels of 
      reactive oxygen species (ROS), interleukin-6 (IL-6), and MMPs. MATERIAL AND 
      METHODS Pelvic floor fibroblasts were obtained from connective tissue from three 
      patients with POP and three normal subjects. Cell proliferation and ROS 
      production were measured using a cell counting kit-8 (CCK-8) assay and flow 
      cytometry. Levels of interleukin-6 (IL-6), klotho, metalloproteinase-1 (MMP-1), 
      MMP-3, extracellular signal-regulated kinases 1/2 (ERK1/2), and p-ERK1/2 were 
      measured by enzyme-linked immunoassay (ELISA), quantitative real-time polymerase 
      chain reaction (qRT-PCR), and Western blot. RESULTS In cultured pelvic floor 
      fibroblasts from patients with POP, the expression of klotho protein and klotho 
      mRNA were significantly down-regulated in fibroblasts from patients with POP 
      compared with normal fibroblasts. Klotho supplementation in cultured fibroblasts 
      for patients with POP included increased cell growth, reduced expression of ROS 
      reduction, and reduced the secretion of IL-6. Using qRT-PCR and Western blot, 
      klotho supplementation of fibroblasts from patients with POP increased cell 
      growth and reduced the levels of IL-6 and ROS in a dose-dependent way. 
      CONCLUSIONS Klotho protein reduced the expression of MMP-1 and MMP-3 in 
      fibroblasts from patients with POP by down-regulating the phosphorylation of 
      ERK1/2.
FAU - Qiu, Jun
AU  - Qiu J
AD  - Department of Gynecology, The International Peace Maternity and Child Health 
      Hospital of Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo 
      Original Diseases, Shanghai, China (mainland).
FAU - Qin, Menglu
AU  - Qin M
AD  - Department of Gynecology, The International Peace Maternity and Child Health 
      Hospital of Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo 
      Original Diseases, Shanghai, China (mainland).
FAU - Fan, Bozhen
AU  - Fan B
AD  - Department of Gynaecology and Obstetrics, Putuo Hospital Affiliated to Shanghai 
      University of Traditional Chinese Medicine, Shanghai, China (mainland).
FAU - Chen, Xinliang
AU  - Chen X
AD  - Department of Gynecology, The International Peace Maternity and Child Health 
      Hospital of Shanghai Jiaotong University, Shanghai Key Laboratory of Embryo 
      Original Diseases, Shanghai, China (mainland).
LA  - eng
PT  - Journal Article
DEP - 20190522
PL  - United States
TA  - Med Sci Monit
JT  - Medical science monitor : international medical journal of experimental and 
      clinical research
JID - 9609063
RN  - 0 (Interleukin-6)
RN  - 0 (Reactive Oxygen Species)
RN  - 9007-34-5 (Collagen)
RN  - EC 3.2.1.31 (Glucuronidase)
RN  - EC 3.2.1.31 (Klotho Proteins)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Cells, Cultured
MH  - China
MH  - Collagen/metabolism
MH  - Down-Regulation
MH  - Extracellular Matrix/metabolism
MH  - Female
MH  - Fibroblasts/metabolism
MH  - Glucuronidase/genetics/*metabolism
MH  - Humans
MH  - Interleukin-6/metabolism
MH  - Klotho Proteins
MH  - MAP Kinase Signaling System/physiology
MH  - Matrix Metalloproteinase 1/genetics/*metabolism
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Middle Aged
MH  - Pelvic Floor
MH  - Pelvic Organ Prolapse/*metabolism
MH  - Phosphorylation
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
PMC - PMC6542300
COIS- Conflict of interest None.
EDAT- 2019/05/23 06:00
MHDA- 2019/12/18 06:00
PMCR- 2019/05/22
CRDT- 2019/05/23 06:00
PHST- 2019/05/23 06:00 [entrez]
PHST- 2019/05/23 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/05/22 00:00 [pmc-release]
AID - 913623 [pii]
AID - 10.12659/MSM.913623 [doi]
PST - epublish
SO  - Med Sci Monit. 2019 May 22;25:3815-3824. doi: 10.12659/MSM.913623.