PMID- 33352936
OWN - NLM
STAT- MEDLINE
DCOM- 20210316
LR  - 20240330
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 24
DP  - 2020 Dec 18
TI  - Linking ABCC6 Deficiency in Primary Human Dermal Fibroblasts of PXE Patients to 
      p21-Mediated Premature Cellular Senescence and the Development of a 
      Proinflammatory Secretory Phenotype.
LID - 10.3390/ijms21249665 [doi]
LID - 9665
AB  - Pseudoxanthoma elasticum (PXE) is a rare autosomal-recessive disorder that is 
      mainly caused by mutations in the ATP-binding cassette sub-family C member 6 
      (ABCC6) gene. Clinically PXE is characterized by a loss of skin elasticity, 
      arteriosclerosis or visual impairments. It also shares some molecular 
      characteristics with known premature aging syndromes like the Hutchinson-Gilford 
      progeria syndrome (HGPS). However, little is known about accelerated aging 
      processes, especially on a cellular level for PXE now. Therefore, this study was 
      performed to reveal a potential connection between premature cellular aging and 
      PXE pathogenesis by analyzing cellular senescence, a corresponding secretory 
      phenotype and relevant factors of the cell cycle control in primary human dermal 
      fibroblasts of PXE patients. Here, we could show an increased 
      senescence-associated beta-galactosidase (SA-beta-Gal) activity as well as an increased 
      expression of proinflammatory factors of a senescence-associated secretory 
      phenotype (SASP) like interleukin 6 (IL6) and monocyte chemoattractant protein-1 
      (MCP1). We further observed an increased gene expression of the cyclin-dependent 
      kinase inhibitor (CDKI) p21, but no simultaneous induction of p53 gene 
      expression. These data indicate that PXE is associated with premature cellular 
      senescence, which is possibly triggered by a p53-independent p21-mediated 
      mechanism leading to a proinflammatory secretory phenotype.
FAU - Tiemann, Janina
AU  - Tiemann J
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Wagner, Thomas
AU  - Wagner T
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Lindenkamp, Christopher
AU  - Lindenkamp C
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Plumers, Ricarda
AU  - Plumers R
AUID- ORCID: 0000-0003-2265-9415
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Faust, Isabel
AU  - Faust I
AUID- ORCID: 0000-0002-2234-9196
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Knabbe, Cornelius
AU  - Knabbe C
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
FAU - Hendig, Doris
AU  - Hendig D
AUID- ORCID: 0000-0002-3660-6923
AD  - Institut fur Laboratoriums-und Transfusionsmedizin, Herz-und Diabeteszentrum 
      Nordrhein-Westfalen, Universitatsklinik der Ruhr-Universitat Bochum, 32545 Bad 
      Oeynhausen, Germany.
LA  - eng
GR  - K107-16/FORUM Research Grant of the Ruhr-University Bochum/
PT  - Journal Article
DEP - 20201218
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (ABCC6 protein, human)
RN  - 0 (Biomarkers)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p21)
RN  - 0 (Lamin Type B)
RN  - 0 (Multidrug Resistance-Associated Proteins)
RN  - 0 (RNA, Messenger)
RN  - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27)
SB  - IM
MH  - Biomarkers
MH  - Cellular Senescence/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p21/*metabolism
MH  - Cyclin-Dependent Kinase Inhibitor p27/genetics
MH  - Dermis/*cytology
MH  - Fibroblasts/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Lamin Type B/genetics
MH  - Multidrug Resistance-Associated Proteins/*deficiency
MH  - Mutation
MH  - Phenotype
MH  - Pseudoxanthoma Elasticum/*etiology/*metabolism/pathology
MH  - RNA, Messenger
PMC - PMC7766446
OTO - NOTNLM
OT  - cellular senescence
OT  - pseudoxanthoma elasticum
OT  - senescence-associated secretory phenotype
COIS- The authors declare no conflict of interest.
EDAT- 2020/12/24 06:00
MHDA- 2021/03/17 06:00
PMCR- 2020/12/18
CRDT- 2020/12/23 01:02
PHST- 2020/11/18 00:00 [received]
PHST- 2020/12/16 00:00 [revised]
PHST- 2020/12/17 00:00 [accepted]
PHST- 2020/12/23 01:02 [entrez]
PHST- 2020/12/24 06:00 [pubmed]
PHST- 2021/03/17 06:00 [medline]
PHST- 2020/12/18 00:00 [pmc-release]
AID - ijms21249665 [pii]
AID - ijms-21-09665 [pii]
AID - 10.3390/ijms21249665 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Dec 18;21(24):9665. doi: 10.3390/ijms21249665.