Universität zu Köln

Auler, Markus, Bergmeier, Vera, Georgieva, Veronika S. ORCID: 0000-0002-9234-2504, Pitzler, Lena, Frie, Christian, Nuechel, Julian, Eckes, Beate, Hinz, Boris and Brachvogel, Bent ORCID: 0000-0002-3923-0554 (2021). miR-127-3p Is an Epigenetic Activator of Myofibroblast Senescence Situated within the MicroRNA-Enriched Dlk1-Dio3-Imprinted Domain on Mouse Chromosome 12. J. Invest. Dermatol., 141 (4). S. 1076 - 1090. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1523-1747

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Abstract

During wound healing, fibroblasts differentiate into nonproliferative contractile myofibroblasts, contribute to skin repair, and eventually undergo apoptosis or become senescent. MicroRNAs are post-transcriptional regulators of gene expression networks that control cell fate and survival and may also regulate senescence. In this study, we determined the regulated microRNAs in myofibroblasts isolated from wounds and analyzed their role in senescent myofibroblast formation. Transcriptome profiling showed that a 200 kilobase pair region of the Dlk1-Dio3.imprinted domain on mouse chromosome 12 encodes for most of the upregulated microRNAs in the entire genome of mouse myofibroblasts. Among those, miR-127-3p induced a myofibroblast-like phenotype associated with a block in proliferation. Molecular analysis revealed that miR-127-3p induced a prolonged cell cycle arrest with unique molecular features of senescence, including the activation of the senescence-associated beta-galactosidase, increase in p53 and p21 levels, inhibition of lamin B1, proliferation factors, and the production of senescence-associated inflammatory and extracellular matrix-remodeling components. Hence, miR-127-3p emerges as an epigenetic activator regulating the transition from repair to remodeling during skin wound healing but may also induce age-related defects, pathological scarring, and fibrosis, all linked to myofibroblast senescence.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Auler, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergmeier, Vera UNSPECIFIED UNSPECIFIED UNSPECIFIED Georgieva, Veronika S. UNSPECIFIED orcid.org/0000-0002-9234-2504 UNSPECIFIED Pitzler, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Frie, Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuechel, Julian UNSPECIFIED UNSPECIFIED UNSPECIFIED Eckes, Beate UNSPECIFIED UNSPECIFIED UNSPECIFIED Hinz, Boris UNSPECIFIED UNSPECIFIED UNSPECIFIED Brachvogel, Bent UNSPECIFIED orcid.org/0000-0002-3923-0554 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-573963
DOI:	10.1016/j.jid.2020.11.011
Journal or Publication Title:	J. Invest. Dermatol.
Volume:	141
Number:	4
Page Range:	S. 1076 - 1090
Date:	2021
Publisher:	ELSEVIER SCIENCE INC
Place of Publication:	NEW YORK
ISSN:	1523-1747
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MECHANICAL MEMORY; EXPRESSION; DIFFERENTIATION; APOPTOSIS; P21 Multiple languages Dermatology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/57396