Growth and differentiation factor 11 (GDF11): Functions in the regulation of erythropoiesis and cardiac regeneration

Luc Rochette (1, 2) , Marianne Zeller (1, 2) , Yves Cottin (1) , Catherine Vergely (1, 2)

1 PEC2 - Physiopathologie et épidémiologie cérébro-cardiovasculaire [Dijon]
2 LPPCM - Laboratoire de Physiopathologie et Pharmacologie Cardio-Métaboliques (U866, Lipides et nutrition, équipe 5)

Members of the TGF-β superfamily transduce their signals through type I and II receptor serine/threonine kinases. The binding of activins to activin type IIA (ActRIIA) or type IIB (ActRIIB) receptors induces the recruitment and phosphorylation of an activin type I receptor (ALK4 and/or ALK7), which then phosphorylates the Smad2 and Smad3 intracellular signaling proteins. The regulation of members of the TGF-β family is known to be complex, because many proteins able to bind the ligands and inhibit their activities have been identified. Growth and differentiation factor 11 (Gdf11) belongs to the TGF-β family. GDF11, like other members of the TGF-β superfamily, is produced from precursor proteins by proteolytic processing. Recent studies have reported that GDF11-ActRIIB-Smad2/3-dependent signaling is a key regulatory mechanism in proliferating erythroid precursors as it controls their late-stage maturation. In mammalian tissues, aging is typically accompanied by a progressive loss of homeostasis and impaired regenerative potential. The administration of GDF11 is effective in experimental cardiac hypertrophy, and the identification of GDF11 as a "rejuvenating factor" opens up perspectives for the treatment of age-related cardiac dysfunction. Recent studies of the heart, skeletal muscle and central nervous system indicate that exposure to young blood reverses age-related impairments. The molecular mediators of this "rejuvenation" include growth factors such as GDF11 and cytokines such as CCL11. GDF11 and CCL11 are, perhaps, only the first two in a series of circulating molecules that will be found to influence the aging of different tissues; Are CCL11 and GDF11 endogenous factors for an "elixir of youth"?

Mots clés: GDF11; CCL11; erythropoiesis; cardiac regeneration

Domaines: Biochimie, Biologie Moléculaire; Cardiologie et système cardiovasculaire

Luc Rochette, Marianne Zeller, Yves Cottin, Catherine Vergely. Growth and differentiation factor 11 (GDF11): Functions in the regulation of erythropoiesis and cardiac regeneration. Pharmacology and Therapeutics, 2015, 156, pp.26-33. ⟨10.1016/j.pharmthera.2015.10.006⟩. ⟨hal-03434120⟩