Abstract:The anterior pituitary gland comprises five types of endocrine cells plus non-endocrine cells including folliculostellate cells, endothelial cells, and capillary mural cells (pericytes). In addition to being controlled by the hypothalamic-pituitary-target organ axis, the functions of these cells are likely regulated by local cell and extracellular matrix (ECM) interactions. However, these complex interactions are not fully understood. We investigated folliculostellate cell-mediated cell-to-cell interaction. Us… Show more
“…1c). As was the case in our previous report [28], TGFβ receptor II mRNA was detected in parenchymal cells, perivascular cells, and endothelial cells. Double staining showed that parenchymal cells were co-stained with S100 protein and that perivascular cells were co-stained with desmin (Fig.…”
Section: Discussionsupporting
confidence: 83%
“…It is a potent regulator of ECM synthesis, in which signaling stimulates synthesis of ECM components [20, 28, 29]. Indeed, our past and present findings show that TGFβ2 induced fibromodulin and collagen synthesis in pericytes [28].…”
Section: Discussionmentioning
confidence: 79%
“…Our previous study using a 3D cell culture system of rat anterior pituitary cells showed that TGFβ2 acts on pericytes and induces type I and III collagen synthesis [28]. In the present experiment, we used the same technique to evaluate the effect of TGFβ2 on fibromodulin expression.…”
Section: Discussionmentioning
confidence: 99%
“…Folliculostellate cells express various paracrine/autocrine factors [1], whereas pericytes are mural cells of capillaries and are the sole collagen-producing cells in rat anterior pituitary gland [5]. We recently identified a novel cell-to-cell interaction between these cells and discovered that transforming growth factor-beta 2 (TGFβ2) secreted from folliculostellate cells strongly induced collagen synthesis in pericytes [28]. …”
Fibromodulin belongs to the family of small leucine-rich proteoglycans (SLRPs), an active component of extracellular matrix. It directly binds collagens to promote fibrillogenesis and also binds transforming growth factor-beta (TGFβ) to antagonize its actions. Our previous studies of rat anterior pituitary gland revealed that fibromodulin is expressed in folliculostellate cells and pericytes. Although our recent study showed that TGFβ2 secreted from folliculostellate cells induces collagen synthesis in pericytes, the involvement of fibromodulin in TGFβ2-mediated collagen regulation has not been studied. The present study examined the effect of TGFβ2 on fibromodulin synthesis in rat anterior pituitary gland. In situ hybridization for TGFβ receptor II and immunohistological techniques revealed the presence of TGFβ receptor II in folliculostellate cells and pericytes. To confirm canonical TGFβ intracellular signaling, Smad2 immunocytochemistry was performed. Nuclear translocation of Smad2 was observed in folliculostellate cells and pericytes after TGFβ2 treatment. TGFβ2 strongly enhanced fibromodulin mRNA and protein expressions, and TGFβ2-induced mRNA expression was completely blocked by TGFβ receptor I inhibitor (SB431542). These results suggest that folliculostellate cells and pericytes exhibit canonical TGFβ2 signaling, which is associated with fibromodulin production. Thus, this is the first report to show that TGFβ signaling regulates the endogenous TGFβ antagonist fibromodulin in the gland.
“…1c). As was the case in our previous report [28], TGFβ receptor II mRNA was detected in parenchymal cells, perivascular cells, and endothelial cells. Double staining showed that parenchymal cells were co-stained with S100 protein and that perivascular cells were co-stained with desmin (Fig.…”
Section: Discussionsupporting
confidence: 83%
“…It is a potent regulator of ECM synthesis, in which signaling stimulates synthesis of ECM components [20, 28, 29]. Indeed, our past and present findings show that TGFβ2 induced fibromodulin and collagen synthesis in pericytes [28].…”
Section: Discussionmentioning
confidence: 79%
“…Our previous study using a 3D cell culture system of rat anterior pituitary cells showed that TGFβ2 acts on pericytes and induces type I and III collagen synthesis [28]. In the present experiment, we used the same technique to evaluate the effect of TGFβ2 on fibromodulin expression.…”
Section: Discussionmentioning
confidence: 99%
“…Folliculostellate cells express various paracrine/autocrine factors [1], whereas pericytes are mural cells of capillaries and are the sole collagen-producing cells in rat anterior pituitary gland [5]. We recently identified a novel cell-to-cell interaction between these cells and discovered that transforming growth factor-beta 2 (TGFβ2) secreted from folliculostellate cells strongly induced collagen synthesis in pericytes [28]. …”
Fibromodulin belongs to the family of small leucine-rich proteoglycans (SLRPs), an active component of extracellular matrix. It directly binds collagens to promote fibrillogenesis and also binds transforming growth factor-beta (TGFβ) to antagonize its actions. Our previous studies of rat anterior pituitary gland revealed that fibromodulin is expressed in folliculostellate cells and pericytes. Although our recent study showed that TGFβ2 secreted from folliculostellate cells induces collagen synthesis in pericytes, the involvement of fibromodulin in TGFβ2-mediated collagen regulation has not been studied. The present study examined the effect of TGFβ2 on fibromodulin synthesis in rat anterior pituitary gland. In situ hybridization for TGFβ receptor II and immunohistological techniques revealed the presence of TGFβ receptor II in folliculostellate cells and pericytes. To confirm canonical TGFβ intracellular signaling, Smad2 immunocytochemistry was performed. Nuclear translocation of Smad2 was observed in folliculostellate cells and pericytes after TGFβ2 treatment. TGFβ2 strongly enhanced fibromodulin mRNA and protein expressions, and TGFβ2-induced mRNA expression was completely blocked by TGFβ receptor I inhibitor (SB431542). These results suggest that folliculostellate cells and pericytes exhibit canonical TGFβ2 signaling, which is associated with fibromodulin production. Thus, this is the first report to show that TGFβ signaling regulates the endogenous TGFβ antagonist fibromodulin in the gland.
“…Quantitative real-time PCR and RT-PCR was performed as described in our previous report [8,13]. The primers used to amplify cDNA fragments were listed in Table 1.…”
Section: Real-time Pcr and Reverse Transcription (Rt)-pcrmentioning
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