PMID- 30892936
OWN - NLM
STAT- MEDLINE
DCOM- 20200213
LR  - 20240418
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 316
IP  - 6
DP  - 2019 Jun 1
TI  - Cyp1b1-deficient retinal astrocytes are more proliferative and migratory and are 
      protected from oxidative stress and inflammation.
PG  - C767-C781
LID - 10.1152/ajpcell.00021.2019 [doi]
AB  - Astrocytes (ACs) are the most abundant cells in the central nervous system. 
      Retinal ACs play an important role in maintaining the integrity of retinal 
      neurovascular function, and their dysfunction contributes to the pathogenesis of 
      various eye diseases including diabetic retinopathy. Cytochrome P450 1B1 (CYP1B1) 
      expression in the neurovascular structures of the central nervous system 
      including ACs has been reported. We previously showed that CYP1B1 expression is a 
      key regulator of redox homeostasis in retinal vascular cells. Its deficiency in 
      mice resulted in increased oxidative stress and attenuation of angiogenesis in 
      vivo and proangiogenic activity of retinal vascular cells in vitro. Here, using 
      retinal ACs prepared from wild-type (Cyp1b1(+/+)) and Cyp1b1-deficient 
      (Cyp1b1(-/-)) mice, we determined the impact of Cyp1b1 expression on retinal AC 
      function. We showed that Cyp1b1(-/-) retinal ACs were more proliferative and 
      migratory. These cells also produced increased amounts of fibronectin and its 
      receptors, alpha(v)beta(3)- and alpha(5)beta(1)-integrin. These results were consistent with 
      the increased adhesive properties of Cyp1b1(-/-) ACs and their lack of ability to 
      form a network in Matrigel. This was reversed by reexpression of Cyp1b1 in 
      Cyp1b1(-/-) ACs. Although no significant changes were observed in Akt/SRC/MAPK 
      signaling pathways, production of inflammatory mediators bone morphogenetic 
      protein-7 (BMP-7) and monocyte chemoattractant protein-1 (MCP-1) was decreased in 
      Cyp1b1(-/-) ACs. Cyp1b1(-/-) ACs also showed increased levels of connexin 43 
      phosphorylation and cluster of differentiation 38 expression when challenged with 
      H(2)O(2). These results are consistent with increased proliferation and 
      diminished oxidative stress in Cyp1b1(-/-) cells. Thus, Cyp1b1 expression in ACs 
      plays an important role in retinal neurovascular homeostasis.
FAU - Falero-Perez, Juliana
AU  - Falero-Perez J
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin School 
      of Medicine and Public Health , Madison, Wisconsin.
FAU - Sorenson, Christine M
AU  - Sorenson CM
AD  - Department of Pediatrics, University of Wisconsin School of Medicine and Public 
      Health , Madison, Wisconsin.
FAU - Sheibani, Nader
AU  - Sheibani N
AD  - Department of Ophthalmology and Visual Sciences, University of Wisconsin School 
      of Medicine and Public Health , Madison, Wisconsin.
AD  - Department of Cell and Regenerative Biology, University of Wisconsin School of 
      Medicine and Public Health , Madison, Wisconsin.
AD  - Department of Biomedical Engineering, University of Wisconsin School of Medicine 
      and Public Health , Madison, Wisconsin.
LA  - eng
GR  - P30 CA014520/CA/NCI NIH HHS/United States
GR  - R24 EY022883/EY/NEI NIH HHS/United States
GR  - T32 ES007015/ES/NIEHS NIH HHS/United States
GR  - P30 EY016665/EY/NEI NIH HHS/United States
GR  - R01 EY026078/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20190320
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Inflammation Mediators)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - EC 1.14.14.1 (Cyp1b1 protein, mouse)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1B1)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/*metabolism
MH  - Cell Movement/drug effects/physiology
MH  - Cell Proliferation/drug effects/*physiology
MH  - Cells, Cultured
MH  - Cytochrome P-450 CYP1B1/*biosynthesis
MH  - Hydrogen Peroxide/toxicity
MH  - Inflammation/metabolism/prevention & control
MH  - Inflammation Mediators/antagonists & inhibitors/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Oxidative Stress/drug effects/*physiology
MH  - Retinal Vessels/cytology/drug effects/*metabolism
PMC - PMC6620579
OTO - NOTNLM
OT  - cell adhesion
OT  - extracellular matrix proteins
OT  - inflammation
OT  - oxidative stress
OT  - thrombospondins
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2019/03/21 06:00
MHDA- 2020/02/14 06:00
PMCR- 2020/06/01
CRDT- 2019/03/21 06:00
PHST- 2019/03/21 06:00 [pubmed]
PHST- 2020/02/14 06:00 [medline]
PHST- 2019/03/21 06:00 [entrez]
PHST- 2020/06/01 00:00 [pmc-release]
AID - C-00021-2019 [pii]
AID - 10.1152/ajpcell.00021.2019 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2019 Jun 1;316(6):C767-C781. doi: 
      10.1152/ajpcell.00021.2019. Epub 2019 Mar 20.