Thy-1 Expression in Human Fibroblast Subsets Defines Myofibroblastic or Lipofibroblastic Phenotypes

Abstract

Fibroblasts represent a dynamic population of cells, exhibiting functional heterogeneity within and among tissues. Fibroblast heterogeneity also results from phenotypic differences and may arise from activation or differentiation processes taking place in the cells. We previously reported that human fibroblasts were heterogeneous with respect to surface Thy-1 expression and that separation into Thy-1 ؉ and Thy-1 ؊ subsets resulted in functionally distinct subpopulations, leading to the concept of fibroblast subset specialization. In this report we investigated whether Thy-1 ؉ and/or Thy-1 ؊ fibroblasts were capable of differentiating into myofibroblasts or lipofibroblasts. Fibroblast subsets were used from human myometrium and orbit to test this hypothesis. Only Thy-1 ؉ human myometrial and orbital fibroblasts were capable of myofibroblast differentiation after treatment with TGF␤ or platelet concentrate supernatant, assessed by ␣ smooth muscle actin expression. Interestingly, only Thy-1 ؊ , but not Thy-1 ؉ subsets differentiated to lipofibroblasts, as determined by the accumulation of cytoplasmic lipid droplets after treatment with 15-deoxy-⌬ 12 , 14 -PGJ 2 or ciglitazone. We propose that fibroblast Thy-1 display predetermines lineage to a contractile or lipid-like phenotype in the human myometrium and orbit. This additional distinction between Thy-1 ؉ and Thy-1

Transformujący czynnik wzrostu β1 (TGFβ1) i naczyniowo-śródbłonkowy czynnik wzrostu (VEGF) we krwi ludzi zdrowych i chorych z orbitopatią Gravesa — nowy mechanizm działania glikokortykosteroidów?

“…Enlargement of orbital tissue mass occurs through the accumulation of extracellular matrix (ECM), scar-forming myofibroblasts, and/or fat [34,42,46,49]. TGFb1 is synthesised primarily by platelets, macrophages/monocytes, lymphocytes, fibroblasts, and epithelial cells [50].…”

Thy-1 is expressed in myofibroblasts but not found in hepatic stellate cells following liver injury

“…In addition, lipids rafts, in which GPI-anchored proteins, like Thy-1 are embedded, are often the sites of formation of receptor-adhesion complexes (Hudon-David et al 2007). The fact that Thy-1 + and Thy-1 ¡ lung Wbroblasts behave diVerently suggests that this protein may have a functional role (Koumas et al 2003). Whether or not Thy-1 is responsible for a speciWc action in a subpopulation of liver (myo)Wbroblasts Extrahepatic sources According to recent publications is possible from the bone marrow (Miyata et al 2008) Reported from the bone marrow (Kisseleva et al 2006) remains to be elucidated.…”

“…It was Wrst described in 1964, and subsequently isolated, puriWed, and characterized in rodents (Reif and Allen 1964). Koumas et al (2003) reported that human Wbroblasts are heterogeneous with respect to cell surface Thy-1 expression and that Wbroblasts could be segregated into Thy-1 + and Thy-1 -subsets resulting with distinct functions.…”

Radiotherapy for Graves’ disease. The possible role of low-dose radiotherapy

“…30 Orbital fibroblasts produce GAGs as well as they also differentiate to either myofibroblasts or to lipofibroblasts. 31,32 Immunohistochemical staining of retrobulbar adipose tissue in GO showed an increase HLA-DR expression, an activation of intercellular adhesion molecule 1 (ICAM-1), and a marked infiltration of activated T-cells, especially CD4, and macrophages (CD68) on retrobulbar fat. The perimuscular connective tissue showed an accumulation of CD4/CD8 T-cells, ICAM-1 and B-cells; and retrobulbar muscle tissue exhibit an increase of CD4, CD8 and CD68.…”