Growth Factors Physiology
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Direct answer
Growth factors are polypeptide signals that command cells to proliferate, differentiate or survive, acting mostly on receptor tyrosine kinases: epidermal growth factor (EGF, 53 amino acids, salivary gland and duodenal origin) drives epithelial proliferation; platelet-derived growth factor (PDGF) released from alpha granules recruits smooth muscle and fibroblasts to wounds (and to atherosclerotic plaques); vascular endothelial growth factor (VEGF), induced by hypoxia through HIF-1alpha, sprouts new vessels in the corpus luteum, healing wounds, tumours and the diabetic retina; nerve growth factor (NGF), discovered by Rita Levi-Montalcini (Nobel 1986), sustains sympathetic and sensory neurons; transforming growth factor-beta generally brakes proliferation and drives fibrosis. FGF-23, the endocrine member of the FGF family, is bone's phosphaturic hormone — its production by tumours causes oncogenic osteomalacia.
What you must remember
- Signalling logic: growth factors bind receptor tyrosine kinases, dimerising them; autophosphorylated receptors recruit GRB2-SOS-RAS, switching on the MAP kinase cascade to the nucleus — the same cascade oncogenes hijack.
- EGF system: EGF (53 amino acids) from salivary glands, duodenum and kidney; EGFR (ErbB1/HER1); also inhibits gastric acid secretion — the ancestor fact for EGFR-blocking agents like cetuximab in colorectal and head-neck cancers.
- PDGF: from platelet alpha granules; chemotactic and mitogenic for fibroblasts and vascular smooth muscle; also a chemoattractant in the proliferative phase of wound healing; imatinib inhibits its receptor along with BCR-ABL.
- VEGF: hypoxia (HIF-1alpha) is the master stimulus; acts on endothelium via VEGFR-2; physiological in embryo, corpus luteum and exercising muscle, pathological in diabetic retinopathy and tumours; bevacizumab is the blocking antibody.
- NGF: sustains sympathetic and neural-crest-derived sensory neurons; retrogradely transported, signals through TrkA and p75; raised NGF levels accompany tissue injury and correlate with inflammatory and neuropathic pain states.
- TGF-beta: predominantly anti-proliferative for epithelium, immunosuppressive, and the central pro-fibrotic cytokine in chronic liver, lung and kidney disease — the fibrosis arm worth quoting.
- IGF-1 (somatomedin C): the 70-amino-acid mediator of growth hormone action, produced by liver under GH drive; the marker of acromegaly control and of growth in childhood; IGF-2 is the fetal growth factor.
- FGF-23: from osteocytes, with alpha-Klotho as co-receptor, inhibits proximal-tubular phosphate reabsorption and suppresses calcitriol — excess causes tumour-induced osteomalacia with renal phosphate wasting.
A worked case in angiogenesis
Take the hypoxic border of a healing wound. Falling oxygen activates HIF-1alpha, which accumulates and switches on VEGF transcription; nearby endothelium, through VEGFR-2, degrades its basement membrane, sprouts tip cells, and proliferates along the gradient while PDGF from arriving platelets recruits pericytes and smooth muscle to stabilise the tube. EGF from saliva and epithelial EGFR activation re-epithelialise the surface — the proliferative phase running on schedule.
Now subvert each step. In diabetic retinopathy, retinal ischaemia over-drives VEGF, and fragile new vessels destroy vision — pan-retinal photocoagulation works precisely by ablating the ischaemic retina and removing the VEGF stimulus, while intravitreal anti-VEGF drugs do it pharmacologically. In a tumour, the growing mass co-opts the same sprouting to feed itself; bevacizumab starves the supply line, though tumours eventually recruit alternative angiogenic factors. Every therapy in this list is physiology played in reverse, which is exactly how the integrative viva frames it.
Where students slip
The common slip is lumping growth factors with hormones of the classical endocrine axis: most act paracrinally or autocrally, on neighbouring or self cells, with IGF-1, erythropoietin and FGF-23 the endocrine exceptions worth naming. The second is forgetting directionality — TGF-beta is predominantly anti-proliferative, a brake on epithelial growth and a promoter of fibrosis, not a general growth promoter; quoting its role in fibrosis distinguishes a well-read answer. Third, students separate growth factors from oncology: HER2 (ErbB2) amplification in about 15-20 per cent of breast cancers and BCR-ABL in chronic myeloid leukaemia are growth-factor signalling gone autonomous — trastuzumab and imatinib are receptor-pathway drugs in every sense.
Frequently asked questions
Which growth factor is the principal driver of angiogenesis?
VEGF, induced by hypoxia through HIF-1alpha and acting on endothelial VEGFR-2, sprouting new vessels in physiological settings like the corpus luteum and pathological ones like diabetic retinopathy and tumours.
What is the source and function of PDGF?
Platelet alpha granules release PDGF at injury; it is chemotactic and mitogenic for fibroblasts and vascular smooth muscle, driving granulation tissue in healing and smooth-muscle accumulation in atherosclerosis.
Why does FGF-23 excess cause osteomalacia?
FGF-23 from osteocytes (or tumours) inhibits renal phosphate reabsorption and calcitriol synthesis, producing hypophosphataemia with low 1,25-dihydroxy vitamin D and defective bone mineralisation.
Which growth factor maintains sympathetic neurons, and through which receptor?
Nerve growth factor, discovered by Rita Levi-Montalcini, acting through the TrkA receptor with retrograde transport from target tissues to the soma.
How is growth factor signalling related to oncogenes?
Many proto-oncogenes encode growth factors, their receptors, or downstream messengers such as RAS; mutation or amplification — BCR-ABL, HER2 — makes proliferation ligand-independent, and targeted agents like imatinib and trastuzumab block the resulting pathways.