The plant hormone abscisic acid stimulates the proliferation of human hemopoietic progenitors through the second messenger cyclic ADP-ribose.
Abscisic acid (ABA) is a hormone involved in pivotal physiological functions in higher plants, such as response to abiotic stress and control of seed dormancy and germination. Recently, ABA was demonstrated to be autocrinally produced by human granulocytes, beta pancreatic cells, and mesenchymal stem cells (MSC) and to stimulate cell-specific functions through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). Here we show that ABA expands human uncommitted hemopoietic progenitors (HP) in vitro, through a cADPR-mediated increase of the intracellular calcium concentration ([Ca(2+)](i)). Incubation of CD34(+) cells with micromolar ABA also induces transcriptional effects, which include NF-kappaB nuclear translocation and transcription of genes encoding for several cytokines. Human MSC stimulated with a lymphocyte-conditioned medium produce and release ABA at concentrations sufficient to exert growth-stimulatory effects on co-cultured CD34(+) cells, as demonstrated by the inhibition of colony growth in the presence of an anti-ABA monoclonal antibody. These results provide a remarkable example of conservation of a stress hormone and of its second messenger from plants to humans and identify ABA as a new hemopoietic growth factor involved in the cross-talk between HP and MSC.
Scarfì
Sonia
S
Advanced Biotechnology Center, Genova, Italy.
Fresia
Chiara
C
Ferraris
Chiara
C
Bruzzone
Santina
S
Fruscione
Floriana
F
Usai
Cesare
C
Benvenuto
Federica
F
Magnone
Mirko
M
Podestà
Marina
M
Sturla
Laura
L
Guida
Lucrezia
L
Albanesi
Ennio
E
Damonte
Gianluca
G
Salis
Annalisa
A
De Flora
Antonio
A
Zocchi
Elena
E
D000040:Abscisic Acid / Q000378:metabolism / Q000494:pharmacology*; D018952:Antigens, CD34 / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D036563:Cyclic ADP-Ribose / Q000378:metabolism*; D016207:Cytokines / Q000187:drug effects / Q000235:genetics; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D010937:Plant Growth Regulators / Q000494:pharmacology; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology
D018952:Antigens, CD34; D017077:Culture Media, Conditioned; D016207:Cytokines; D016328:NF-kappa B; D010937:Plant Growth Regulators; D036563:Cyclic ADP-Ribose; D000040:Abscisic Acid; D002118:Calcium