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Vasoprotective effect of PDGF-CC mediated by HMOX1 rescues retinal degeneration
Chang He1, Chen Zhao2, Anil Kumar1
1State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou 510060, People's Republic of China;
Insights
Platelet-derived growth factor C (PDGF-CC) protects blood vessels from degeneration. This study reveals PDGF-CC
Area of Science:
- Vascular Biology
- Regenerative Medicine
- Cell Signaling
Background:
- Blood vessel degeneration is a key factor in many diseases.
- Developing strategies for vascular protection and survival is crucial.
- Platelet-derived growth factor C (PDGF-CC) role in vascular health requires further elucidation.
Purpose of the Study:
- To investigate the role of PDGF-CC in vascular protection and survival.
- To explore the therapeutic potential of PDGF-CC in degenerative diseases.
Main Methods:
- Utilized various animal models and cultured cells.
- Genetic deletion of PDGF-CC to assess its necessity.
- Administered PDGF-CC protein in disease models.
- Investigated the role of heme oxygenase-1 (HMOX1) and PDGF receptors (PDGFR-α, PDGFR-β).
Main Results:
- PDGF-CC deficiency worsened blood vessel degeneration in animal models.
- PDGF-CC treatment improved retinal blood vessel survival and rescued degeneration in retinitis pigmentosa models.
- Heme oxygenase-1 (HMOX1) activity is essential for PDGF-CC's protective effects.
- Both PDGFR-α and PDGFR-β are required for PDGF-CC's vasoprotective function.
Conclusions:
- PDGF-CC is a potent factor for vascular protection and survival.
- PDGF-CC, via HMOX1 and PDGF receptors, plays a critical role in maintaining blood vessel integrity.
- PDGF-CC holds therapeutic promise for treating degenerative vascular diseases.
Abstract:
Blood vessel degeneration is critically involved in nearly all types of degenerative diseases. Therefore strategies to enhance blood vessel protection and survival are highly needed. In this study, using different animal models and cultured cells, we show that PDGF-CC is a potent vascular protective and survival factor. PDGF-CC deficiency by genetic deletion exacerbated blood vessel regression/degeneration in various animal models. Importantly, treatment with PDGF-CC protein not only increased the survival of retinal blood vessels in a model of oxygen-induced blood vessel regression but also markedly rescued retinal and blood vessel degeneration in a disease model of retinitis pigmentosa. Mechanistically, we revealed that heme oxygenase-1 (HMOX1) activity is critically required for the vascular protective/survival effect of PDGF-CC, because blockade of HMOX1 completely abolished the protective effect of PDGF-CC in vitro and in vivo. We further found that both PDGF receptors, PDGFR-β and PDGFR-α, are required for the vasoprotective effect of PDGF-CC. Thus our data show that PDGF-CC plays a pivotal role in maintaining blood vessel survival and may be of therapeutic value in treating various types of degenerative diseases.
