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001-es BibID:	BIBFORM082549
035-os BibID:	(PMID)31405954
Első szerző:	Patsalos, Andreas
Cím:	The BACH1-HMOX1 Regulatory Axis Is Indispensable for Proper Macrophage Subtype Specification and Skeletal Muscle Regeneration / Andreas Patsalos, Petros Tzerpos, Laszlo Halasz, Gergely Nagy, Attila Pap, Nikolas Giannakis, Konstantina Lyroni, Vasiliki Koliaraki, Eva Pintye, Balazs Dezso, George Kollias, Charalampos G. Spilianakis, Laszlo Nagy
Dátum:	2019
ISSN:	0022-1767 1550-6606
Megjegyzések:	The infiltration and subsequent in situ subtype specification of monocytes to effector/inflammatory and repair macrophages is indispensable for tissue repair upon acute sterile injury. However, the chromatin-level mediators and regulatory events controlling this highly dynamic macrophage phenotype switch are not known. In this study, we used a murine acute muscle injury model to assess global chromatin accessibility and gene expression dynamics in infiltrating macrophages during sterile physiological inflammation and tissue regeneration. We identified a heme-binding transcriptional repressor, BACH1, as a novel regulator of this process. Bach1 knockout mice displayed impaired muscle regeneration, altered dynamics of the macrophage phenotype transition, and transcriptional deregulation of key inflammatory and repair-related genes. We also found that BACH1 directly binds to and regulates distal regulatory elements of these genes, suggesting a novel role for BACH1 in controlling a broad spectrum of the repair response genes in macrophages upon injury. Inactivation of heme oxygenase-1 (Hmox1), one of the most stringently deregulated genes in the Bach1 knockout in macrophages, impairs muscle regeneration by changing the dynamics of the macrophage phenotype switch. Collectively, our data suggest the existence of a heme-BACH1--HMOX1 regulatory axis, that controls the phenotype and function of the infiltrating myeloid cells upon tissue damage, shaping the overall tissue repair kinetics.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk
Megjelenés:	Journal of Immunology. - 203 : 6 (2019), p. 1532-1547. -
További szerzők:	Tzerpos, Petros (1982-) (molekuláris biológus) Halász László (1989-) (molekuláris biológus) Nagy Gergely (1986-) (molekuláris biológus) Pap Attila (1980-) (biológus) Giannakis, Nikolas Lyroni, Konstantina Koliaraki, Vasiliki Pintye Éva (1955-) (fizikus) Dezső Balázs (1951-) (pathológus) Kollias, George Spilianakis, Charalampos G. Nagy László (1966-) (molekuláris sejtbiológus, biokémikus)
Pályázati támogatás:	124298 OTKA 126885 OTKA KKP129909 OTKA 20428-3/2018/FEKUTSTRAT FIKP Horizon2020 GA: 622934 Egyéb PD124843 OTKA "Nuclear Receptor-Network" Consortium Grant PITN-GA-2013-606806 FP7
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