LIF, a mitogen for choroidal endothelial cells, protects the choriocapillaris: implications for prevention of geographic atrophy.
Pin LiQin LiNilima BiswasHong XinTanja DiemerLixian LiuLorena Perez GutierrezGiovanni PaternostroCarlo PiermarocchiSergii DomanskyiRuikang K WangNapoleone FerraraPublished in: EMBO molecular medicine (2021)
In the course of our studies aiming to discover vascular bed-specific endothelial cell (EC) mitogens, we identified leukemia inhibitory factor (LIF) as a mitogen for bovine choroidal EC (BCE), although LIF has been mainly characterized as an EC growth inhibitor and an anti-angiogenic molecule. LIF stimulated growth of BCE while it inhibited, as previously reported, bovine aortic EC (BAE) growth. The JAK-STAT3 pathway mediated LIF actions in both BCE and BAE cells, but a caspase-independent proapoptotic signal mediated by cathepsins was triggered in BAE but not in BCE. LIF administration directly promoted activation of STAT3 and increased blood vessel density in mouse eyes. LIF also had protective effects on the choriocapillaris in a model of oxidative retinal injury. Analysis of available single-cell transcriptomic datasets shows strong expression of the specific LIF receptor in mouse and human choroidal EC. Our data suggest that LIF administration may be an innovative approach to prevent atrophy associated with AMD, through protection of the choriocapillaris.
Keyphrases
- endothelial cells
- optical coherence tomography
- single cell
- induced apoptosis
- rna seq
- protein kinase
- heart failure
- high glucose
- acute myeloid leukemia
- cell death
- machine learning
- oxidative stress
- high throughput
- left ventricular
- signaling pathway
- cell proliferation
- pulmonary arterial hypertension
- pulmonary artery
- big data
- endoplasmic reticulum stress