PMID- 30913036
OWN - NLM
STAT- MEDLINE
DCOM- 20191213
LR  - 20210213
IS  - 2191-0286 (Electronic)
IS  - 0792-6855 (Linking)
VI  - 30
IP  - 3
DP  - 2019 Mar 26
TI  - Evaluation of inductive effects of different concentrations of cyclosporine A on 
      MMP-1, MMP-2, MMP-3, TIMP-1, and TIMP-2 in fetal and adult human gingival 
      fibroblasts.
LID - 10.1515/jbcpp-2018-0176 [doi]
AB  - Background The etiology of gingival overgrowth due to cyclosporine A (CsA) is 
      still unknown. The aim of this study was to determine the possible role of matrix 
      metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) on extra-cellular 
      matrix (ECM) homeostasis when treated with different levels of CsA and its 
      difference between fetal and adult human gingival fibroblasts (HGFs). Methods 
      Each group of cells (adult and fetal) was cultured in 40 wells that consisted of 
      four different CsA treatment concentrations. Every 10 wells were treated with 0, 
      50, 100, and 150 ng/mL of CsA which makes a total of 80 wells. Supernatants of 
      every well were used to determine the concentration of MMPs and TIMPs using the 
      Elisa kits from Boster, CA, USA. Results MMP-1 level increased with the treatment 
      of CsA when treated with 50 and 150 ng/mL of CsA (p = 0.02 and p = 0.04) as 
      TIMP-1 decreased (p < 0.0001) in adult group; while in the fetal group, TIMP-1 
      level increased with treatment of 150 ng/mL (p < 0.0001). MMP-2 level increased 
      in both adult and fetal groups (p < 0.0001). MMP-3 level decreased in adult group 
      (p < 0.0001) but went up in fetal HGFs (p = 0.01) when treated with 150 ng/mL 
      CsA. TIMP-2 level increased in all wells significantly when treated with CsA (p < 
      0.0001). The study showed that CsA affects secretion of MMPs and TIMPs. MMP-1 
      increment and TIMP-1 decrement were observed, which indicate more degradation of 
      ECM. This may be due to single donor use in this study. TIMP-2 and MMP-2 were 
      both more active when treated with CsA which may be due to the gelatinase 
      activity of them and that in CsA gingival overgrowth. There was more inflammation 
      rather than fibrosis.
FAU - Nazemisalman, Bahareh
AU  - Nazemisalman B
AD  - Pedodontics Department, Dental School, Zanjan University of Medical Sciences, 
      Zanjan, Iran.
FAU - Sajedinejad, Neda
AU  - Sajedinejad N
AD  - Periodontics Department, Zanjan University of Medical Science, Zanjan, Iran.
FAU - Darvish, Shayan
AU  - Darvish S
AD  - Pardis Health Center, Shahid Beheshti University of Medical Sciences, Tehran, 
      Iran.
FAU - Vahabi, Surena
AU  - Vahabi S
AD  - Periodontics Department, School of Dentistry, Shahid Beheshti University of 
      Medical Sciences, Tehran, Iran.
FAU - Gudarzi, Hoda
AU  - Gudarzi H
AD  - Department of Virology, School of Public Health, Tehran University of Medical 
      Sciences, Tehran, Iran.
LA  - eng
PT  - Journal Article
DEP - 20190326
PL  - Germany
TA  - J Basic Clin Physiol Pharmacol
JT  - Journal of basic and clinical physiology and pharmacology
JID - 9101750
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (TIMP1 protein, human)
RN  - 0 (TIMP2 protein, human)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 83HN0GTJ6D (Cyclosporine)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.17 (MMP3 protein, human)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.7 (MMP1 protein, human)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - Adult
MH  - Cell Line
MH  - Cyclosporine/*toxicity
MH  - Dose-Response Relationship, Drug
MH  - Extracellular Matrix/*drug effects/metabolism
MH  - Fibroblasts/*drug effects/metabolism
MH  - Gingiva/*drug effects/embryology/growth & development/metabolism
MH  - Gingival Overgrowth/chemically induced/embryology/metabolism
MH  - Humans
MH  - Immunosuppressive Agents/*toxicity
MH  - Matrix Metalloproteinase 1/metabolism
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Matrix Metalloproteinase 3/metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Tissue Inhibitor of Metalloproteinase-1/metabolism
MH  - Tissue Inhibitor of Metalloproteinase-2/metabolism
MH  - Tissue Inhibitor of Metalloproteinases/*metabolism
OTO - NOTNLM
OT  - cyclosporine A (CsA)
OT  - gingival fibroblast
OT  - gingival overgrowth
OT  - matrix metalloproteinases (MMPs)
OT  - tissue inhibitors of MMPs (TIMPs)
EDAT- 2019/03/27 06:00
MHDA- 2019/12/18 06:00
CRDT- 2019/03/27 06:00
PHST- 2018/10/05 00:00 [received]
PHST- 2019/01/10 00:00 [accepted]
PHST- 2019/03/27 06:00 [pubmed]
PHST- 2019/12/18 06:00 [medline]
PHST- 2019/03/27 06:00 [entrez]
AID - jbcpp-2018-0176 [pii]
AID - 10.1515/jbcpp-2018-0176 [doi]
PST - epublish
SO  - J Basic Clin Physiol Pharmacol. 2019 Mar 26;30(3). doi: 10.1515/jbcpp-2018-0176.