title: Aggrecan expression is substantially and abnormally upregulated in Hutchinson-Gilford Progeria Syndrome dermal fibroblasts.
abstract: Hutchinson-Gilford Progeria syndrome (HGPS) is a rare genetic disorder that displays features of segmental aging. It is manifested predominantly in connective tissue, with most prominent histological changes occurring in the skin, cartilage, bone and cardiovascular tissues. Detailed quantitative real time reverse-transcription polymerase chain reaction studies confirmed the previous observation that platelet-derived growth factor A-chain transcripts are consistently elevated 11+/-2- to 13+/-2-fold in two HGPS dermal fibroblast lines compared with age-matched controls. Furthermore, we identified two additional genes with substantially altered transcript levels. Nucleotide pyrophosphatase transcription was virtually shut down with decreased expression of 13+/-3- to 59+/-3-fold in HGPS, whereas aggrecan mRNA was elevated to 24+/-5 times to 41+/-4 times that of chronologically age-matched controls. Aggrecan, normally a component of cartilage and not always detectable in normal fibroblasts cultures, was secreted by HGPS fibroblast lines and was produced as a proteoglycan. This demonstrates that elevated aggrecan expression and its secretion are aberrant features of HGPS. We conclude that HGPS cells can display massively altered transcript levels leading to the secretion of inappropriate protein species.
authors.affiliation: Department of Anatomy and Cellular Biology, Tufts University School of Medicine, Boston, MA, USA.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Lemire
authors.forename: Carrie
authors.initials: C
authors.lastname: Patis
authors.forename: Leslie B
authors.initials: LB
authors.lastname: Gordon
authors.forename: John D
authors.initials: JD
authors.lastname: Sandy
authors.forename: Bryan P
authors.initials: BP
authors.lastname: Toole
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Weiss
mesh_terms: D000199:Actins / Q000235:genetics; D053674:Aggrecans; D002460:Cell Line; D002648:Child; D002675:Child, Preschool; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000502:physiology*; D006801:Humans; D037181:Lectins, C-Type / Q000235:genetics*; D016555:Matched-Pair Analysis; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011371:Progeria / Q000235:genetics / Q000503:physiopathology*; D011755:Pyrophosphatases / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D000199:Actins; D053674:Aggrecans; D011508:Chondroitin Sulfate Proteoglycans; D016326:Extracellular Matrix Proteins; D037181:Lectins, C-Type; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C075278:platelet-derived growth factor A; D011755:Pyrophosphatases; C021899:nucleotide pyrophosphatase