title: Dissecting the impact of Frizzled receptors in Wnt/β-catenin signaling of human mesenchymal stem cells.
abstract: Wnt/β-catenin signaling is of fundamental importance in the regulation of self-renewal, migration/invasion, and differentiation of human mesenchymal stem cells (hMSCs). Because little information is available about the function of Frizzled receptors (Fzds) as the main receptors of Wnt proteins in hMSCs, we first performed comparative Fzd mRNA expression profiling. Fzd9 and Fzd10 were not expressed in hMSCs. While Fzd3 was expressed at low levels in hMSCs, the other Fzds exhibited high expression rates. Activation and repression of Wnt signaling in hMSCs revealed that the expression levels of Fzd1, Fzd6, and Fzd7 are positively correlated with the Wnt/β-catenin activation status, whereas Fzd8 exhibited an inverse relation. For studying the functional relevance of Fzds in Wnt/β-catenin signaling, RNA interference, ectopic expression studies, and rescue approaches were performed in hMSCs carrying a highly sensitive TCF/LEF reporter gene system (Gaussia luciferase). We found that, Fzd1, Fzd5, Fzd7, and Fzd8 are largely involved in Wnt/β-catenin signaling of hMSCs. Moreover, the knockdown of Fzd5 can be compensated by the ectopic expression of Fzd7. Conversely, the ectopic expression of Fzd5 in Fzd7-knockdown hMSCs resulted in a rescue of Wnt/β-catenin signaling, pointing to a functional redundancy of Fzd5 and Fzd7.
authors.affiliation: Department of Obstetrics and Gynecology, Ludwig-Maximilians University, Munich, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kolben
authors.forename: Iris
authors.initials: I
authors.lastname: Peröbner
authors.forename: Katharina
authors.initials: K
authors.lastname: Fernsebner
authors.forename: Felix
authors.initials: F
authors.lastname: Lechner
authors.forename: Claudia
authors.initials: C
authors.lastname: Geissler
authors.forename: Lourdes
authors.initials: L
authors.lastname: Ruiz-Heinrich
authors.forename: Simon
authors.initials: S
authors.lastname: Capovilla
authors.forename: Marianne
authors.initials: M
authors.lastname: Jochum
authors.forename: Peter
authors.initials: P
authors.lastname: Neth
mesh_terms: D000328:Adult; D002478:Cells, Cultured; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051157:Frizzled Receptors; D012333:RNA, Messenger; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin