PMID- 29610861
OWN - NLM
STAT- MEDLINE
DCOM- 20190128
LR  - 20211204
IS  - 1552-5783 (Electronic)
IS  - 0146-0404 (Linking)
VI  - 59
IP  - 5
DP  - 2018 Apr 1
TI  - Integrin-Linked Kinase Controls Choroidal Neovascularization by Recruitment of 
      Endothelial Progenitor Cells.
PG  - 1779-1789
LID - 10.1167/iovs.17-22931 [doi]
AB  - PURPOSE: Vasculogenesis has been shown to contribute to the formation of 
      choroidal neovascularization (CNV). However, the mechanism behind the recruitment 
      of endothelial progenitor cells (EPC) to CNV is not well understood. Therefore, 
      we were interested to know whether integrin-linked kinase (ILK) plays a role in 
      recruiting EPC to CNV, and its possible mechanism. METHODS: We investigated the 
      effect of hypoxia on retinal pigment epithelium (RPE) cells expressing ILK, 
      hypoxia-inducible factor 1alpha (HIF-1alpha), stromal-derived factor-1 (SDF-1), and 
      vascular endothelial growth factor (VEGF), and we further examined the effect of 
      ILK small interfering RNA (siRNA) on their expression. The function of ILK 
      expressed by RPE on EPC in vitro with regard to angiogenic effect was also 
      studied. In vivo, we determined the expression levels of the above factors in 
      CNV. We also examined the role of ILK on their expression, on EPC recruiting, and 
      on the growth of CNV. RESULTS: We found that hypoxia strongly induced the 
      expression of ILK, HIF-1alpha, SDF-1, and VEGF. Moreover, the silencing of ILK 
      attenuated their expression. It also decreased the phosphorylation of protein 
      kinase B (PKB/AKT) and extracellular regulated protein kinases (ERK) and nearly 
      abolished the proliferation, migration, and adhesion of EPC to RPE cells. In 
      vivo, we showed that these factors were upregulated in CNV. Inhibiting the 
      expression of ILK prohibited the "homing" of EPC to CNV lesions and attenuated 
      the growth of CNV. CONCLUSIONS: We demonstrate that ILK controls the development 
      of CNV by regulating the recruitment of EPC to CNV lesions, possibly through 
      ILK-dependent expression of SDF-1 and VEGF in RPE.
FAU - Yang, Xiu-Mei
AU  - Yang XM
AD  - Department of Ophthalmology, PLA Army General Hospital, Beijing, China.
AD  - Department of Ophthalmology, Eye Institute of Ophthalmology of Chinese PLA, 
      Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 
      China.
FAU - Duan, Chun-Guang
AU  - Duan CG
AD  - Department of Orthopaedics, Shenzhen University General Hospital, Shenzhen, 
      Guangzhou Province, China.
FAU - Zhang, Jian
AU  - Zhang J
AD  - Department of Biochemistry and Molecular Biology, Fourth Military Medical 
      University, Xi'an, Shaanxi Province, China.
FAU - Qu, Xiao-Jie
AU  - Qu XJ
AD  - Department of Ophthalmology, Eye Institute of Ophthalmology of Chinese PLA, 
      Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 
      China.
FAU - Wang, Yu-Sheng
AU  - Wang YS
AD  - Department of Ophthalmology, Eye Institute of Ophthalmology of Chinese PLA, 
      Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Invest Ophthalmol Vis Sci
JT  - Investigative ophthalmology & visual science
JID - 7703701
RN  - 0 (CXCL12 protein, human)
RN  - 0 (Chemokine CXCL12)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (VEGFA protein, human)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - EC 2.7.1.- (integrin-linked kinase)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Cell Movement/physiology
MH  - Cell Proliferation/physiology
MH  - Cells, Cultured
MH  - Chemokine CXCL12/metabolism
MH  - Choroidal Neovascularization/*enzymology
MH  - Endothelial Progenitor Cells/*metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Signal-Regulated MAP Kinases/metabolism
MH  - Fluorescein Angiography
MH  - Fluorescent Antibody Technique, Indirect
MH  - Humans
MH  - Hypoxia/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - Phosphorylation
MH  - Protein Serine-Threonine Kinases/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Inbred BN
MH  - Retinal Pigment Epithelium/cytology/enzymology
MH  - Signal Transduction
MH  - Up-Regulation
MH  - Vascular Endothelial Growth Factor A/metabolism
EDAT- 2018/04/04 06:00
MHDA- 2019/01/29 06:00
CRDT- 2018/04/04 06:00
PHST- 2018/04/04 06:00 [entrez]
PHST- 2018/04/04 06:00 [pubmed]
PHST- 2019/01/29 06:00 [medline]
AID - 2677991 [pii]
AID - 10.1167/iovs.17-22931 [doi]
PST - ppublish
SO  - Invest Ophthalmol Vis Sci. 2018 Apr 1;59(5):1779-1789. doi: 
      10.1167/iovs.17-22931.