title: Hypoxia-Induced Let-7d Has a Role in Pericyte Differentiation.
abstract: The microvascular pericyte is an important regulatory cell that maintains tissue homeostasis. One of the mechanisms by which pericytes maintain tissue homeostasis is through the induction of endogenous adaptative changes to stress signals. These adaptations include migration, differentiation and induction of angiogenesis. We have investigated pericyte responses to hypoxic stress (1 % O2) and have reported that pericytes adapt to hypoxia, in part, through changes in endogenous and released microRNAs (miRNAs). Of those miRNAs, Let-7d plays an important role. We exposed pericytes to hypoxia with and without basic fibroblast growth factor (bFGF) in stem cell medium. The expression of Let-7d in pericyte-derived neurospheres was determined. Evidence of differentiation was determined by immunocytochemistry. Hypoxia enhanced pericyte spheres were positive for Let-7d. The transcription factor Sox2, a marker of cell differentiation, was also induced in pericytic spheres. Taken together, our results suggest that pericyte expression of Let-7d in response to hypoxia and bFGF is involved in pericyte differentiation. Thus, for the first time, we propose a pathway for induction of pericyte differentiation. Modulation of this pathway in pericytes may be an important target in tissue repair.
authors.affiliation: Department of Neurology, Medical School, Wayne State University, Elliman Building, Rm 3125, 421 E. Canfield Str., Detroit, MI, 48201, USA. nesenbil@med.wayne.edu.
authors.forename: Nilufer
authors.initials: N
authors.lastname: Esen
authors.affiliation: Department of Neurology, Wayne State University, Detroit, MI, USA.
authors.forename: Anuush
authors.initials: A
authors.lastname: Vejalla
authors.affiliation: Department of Neurology, Wayne State University, Detroit, MI, USA.
authors.forename: Rakhi
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Department of Neurological Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Jesse S
authors.initials: JS
authors.lastname: Treuttner
authors.affiliation: Department of Neurology, Wayne State University, Detroit, MI, USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Dore-Duffy
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D015687:Cell Hypoxia; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D020869:Gene Expression Profiling; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D020286:Pericytes / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D051381:Rats; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular; D013997:Time Factors; D015854:Up-Regulation
chemical_list: C548145:MIRNLET7 microRNA, rat; D035683:MicroRNAs; D055748:SOXB1 Transcription Factors; C527784:Sox2 protein, rat; D016222:Fibroblast Growth Factor 2; D010100:Oxygen
keywords: Differentiation; Hypoxia; Let-7d; Pericytes; microRNA