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2014 ; 5
(1
): e1031
Nephropedia Template TP
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Macrophages commit postnatal endothelium-derived progenitors to angiogenesis and
restrict endothelial to mesenchymal transition during muscle regeneration
#MMPMID24481445
Zordan P
; Rigamonti E
; Freudenberg K
; Conti V
; Azzoni E
; Rovere-Querini P
; Brunelli S
Cell Death Dis
2014[Jan]; 5
(1
): e1031
PMID24481445
show ga
The damage of the skeletal muscle prompts a complex and coordinated response that
involves the interactions of many different cell populations and promotes
inflammation, vascular remodeling and finally muscle regeneration. Muscle
disorders exist in which the irreversible loss of tissue integrity and function
is linked to defective neo-angiogenesis with persistence of tissue necrosis and
inflammation. Here we show that macrophages (MPs) are necessary for efficient
vascular remodeling in the injured muscle. In particular, MPs sustain the
differentiation of endothelial-derived progenitors to contribute to neo-capillary
formation, by secreting pro-angiogenic growth factors. When phagocyte
infiltration is compromised endothelial-derived progenitors undergo a significant
endothelial to mesenchymal transition (EndoMT), possibly triggered by the
activation of transforming growth factor-?/bone morphogenetic protein signaling,
collagen accumulates and the muscle is replaced by fibrotic tissue. Our findings
provide new insights in EndoMT in the adult skeletal muscle, and suggest that
endothelial cells in the skeletal muscle may represent a new target for
therapeutic intervention in fibrotic diseases.