title: CCL5/CCR1 axis regulates multipotency of human adipose tissue derived stromal cells.
abstract: Several potential clinical applications of stem cells rely on their capacity to migrate into sites of inflammation where they contribute to tissue regeneration processes. Inflammatory signals are partially mediated by chemokines acting via their receptors expressed on the target cells. Data concerning the repertoire and biological activities of chemokine receptors in human adipose tissue derived stromal cells (ADSCs) are limited. Here we show that CCR1 is one of the few chemokine receptors expressed in ADSCs at a high level. CCR1 expression varies in ADSCs derived from different donors. It sharply decreases in the early phase of ADSCs in vitro propagation, but further demonstrates relative stability. Expression of CCR1 positively correlates with expression of SOX2, OCT4 and NANOG, transcription factors responsible for maintenance of the stemness properties of the cells. We demonstrate that signaling via CCL5/CCR1 axis triggers migration of ADSCs, activates ERK and AKT kinases, stimulates NFκB transcriptional activity and culminates in increased proliferation of CCR1(+) cells accompanied with up-regulation of SOX2, OCT4 and NANOG expression. Our data suggest that chemokine signaling via CCR1 may be involved in regulation of stemness of ADSCs.
authors.affiliation: Protobios LCC, Mäealuse 4, Tallinn 12618, Estonia.
authors.forename: Mari-Liis
authors.initials: ML
authors.lastname: Kauts
authors.forename: Susan
authors.initials: S
authors.lastname: Pihelgas
authors.forename: Kadri
authors.initials: K
authors.lastname: Orro
authors.forename: Toomas
authors.initials: T
authors.lastname: Neuman
authors.forename: Alla
authors.initials: A
authors.lastname: Piirsoo
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D002469:Cell Separation; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D018946:Chemokine CCL5 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D039902:Multipotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D054389:Receptors, CCR1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D014019:Tissue Donors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D054405:Chemokine CCL3; D018946:Chemokine CCL5; D016328:NF-kappa B; D012333:RNA, Messenger; D054389:Receptors, CCR1; D014157:Transcription Factors