MYDGF promotes pathological and physiological retinal angiogenesis via the Gαi1/3-Gab1-Akt-mTOR signaling

Ke-Ran Li1, Ping-Ping Fu2, Wen Bai1

  • 1Jiangsu Key Laboratory of Molecular Targets and Intervention for Metabolic Diseases, The Affiliated Eye Hospital, Nanjing Medical University, Nanjing, China.

Nature Communications
|June 23, 2026
PubMed

Insights

Myeloid-derived growth factor (MYDGF) drives retinal angiogenesis and vascular homeostasis. This factor is upregulated in conditions like diabetic retinopathy, promoting abnormal blood vessel growth.

Area of Science:

  • Ophthalmology
  • Vascular Biology
  • Molecular Medicine

Background:

  • Retinal neovascularization (RNV) is a major cause of vision loss.
  • The molecular mechanisms driving RNV are not fully understood.

Purpose of the Study:

  • To identify key regulators of retinal vascular dynamics.
  • To elucidate the role of myeloid-derived growth factor (MYDGF) in RNV.

Main Methods:

  • Single-cell RNA sequencing
  • Human patient sample analysis
  • In vitro cell culture assays
  • In vivo mouse models of neovascularization and vascular homeostasis

Main Results:

  • MYDGF is upregulated in retinal endothelial cells during pathological neovascularization.
  • MYDGF promotes endothelial cell proliferation, migration, and sprouting in vitro.
  • Endothelial-specific MYDGF depletion impairs normal and pathological retinal angiogenesis in vivo.
  • MYDGF activates the Akt-mTOR pathway via the Gαi1/3-Gab1 signaling complex.

Conclusions:

  • MYDGF is a critical regulator of retinal angiogenesis.
  • MYDGF plays a dual role in promoting pathological neovascularization and maintaining vascular homeostasis.
  • The Gαi1/3-Gab1-Akt-mTOR axis mediates MYDGF's angiogenic effects.

Related Concept Videos

Regulation of Angiogenesis and Blood Supply01:24

Regulation of Angiogenesis and Blood Supply

Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits.  Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl hydroxylase and factor...
Activation and Inactivation of G Proteins01:22

Activation and Inactivation of G Proteins

Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
Mechanism of Angiogenesis01:10

Mechanism of Angiogenesis

Blood vessel formation starts early during embryonic development, around day 7. In the extraembryonic yolk sac, mesodermal precursor cells called hemangioblast proliferate and differentiate into angioblast. Angioblasts express vascular endothelial growth factor receptor 2 or VEGFR2, which binds VEGF-A, a proangiogenic factor, guiding blood vessel formation. VEGF signaling promotes angioblasts to form a blood island in the developing embryo. Angioblasts further differentiate, giving rise to...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...