Density‐ and proliferation status‐dependent expression of T‐cadherin, a novel lipoprotein‐binding glycoprotein: a function in negative regulation of smooth muscle cell growth?

Abstract

The atypical low density lipoprotein (LDL) binding proteins (M r 105 and 130 kDa ; p105 and p130) in human aortic medial membranes and cultured human and rat aortic smooth muscle cells (SMC) have recently been identified as the cell adhesion glycoprotein T-cadherin. Although cadherins are generally recognized to be important regulators of morphogenesis, the function of T-cadherin in the vasculature is poorly understood. This study has examined the relationship between expression of T-cadherin and the density and proliferation status of SMC. T-cadherin (p105 and p130) levels in SMC lysates were measured on Western blots using ligand-binding techniques. T-cadherin expression was dependent upon cell density, and maximal levels were achieved at confluency. T-cadherin levels were reversibly modulated by switching cultures between serumfree (upmodulation) and serum-containing (downmodulation) conditions. Platelet-derived growth factor (PDGF)-BB, epidermal growth factor (EGF) or insulin-like growth factor (IGF) elicited a dose-and time-dependent downmodulation that was reversible after transfer of SMC to growth factor-free medium. Our results support the hypothesis that T-cadherin may function as a negative determinant of cell growth.z 1998 Federation of European Biochemical Societies.

T-Cadherin-Mediated Cell Growth Regulation Involves G2 Phase Arrest and Requires p21CIP1/WAF1 Expression

“…These results suggested that T-cadherin expression might be regulated by culture conditions in vitro. Previous studies have demonstrated that growth factors, confluence, and serum deprivation all modulate T-cadherin expression in other cell types (37). Similar to these results, we found that T-cadherin expression increases in primary astrocytes in vitro in response to conditions that promote growth arrest (serum starvation and contact inhibition).…”

Identification of T-cadherin as a Novel Target of DNA Methyltransferase 3B and Its Role in the Suppression of Nerve Growth Factor-mediated Neurite Outgrowth in PC12 Cells

“…Interestingly, T-Cad can also function as a receptor for low density lipoprotein and adiponection/Acrp30 (26,27). T-Cad is down-regulated by growth factors such as IGF, EGF, and bDGF in smooth muscle cells (28). The molecular mechanism for its down-regulation by these growth factors has not been elucidated.…”

FGF2 induces RANKL gene expression as well as IL1β regulated MHC class II in human bone marrow-derived mesenchymal progenitor stromal cells

“…Immunoblotting of whole cell lysates was performed as described previously. 33 The following primary antibodies were used: rabbit antiphospho thr202/tyr204 -ERK1/2, rabbit antiphospho ser473 -Akt, rabbit antiphospho thr180/tyr182 -p38MAPK (Cell Signaling Technology) and goat anti-GAPDH (Abcam, UK) as the internal protein loading control. Secondary HRP-conjugated goat antirabbit IgG (Southern Biotechnology) or donkey antigoat IgG (Santa Cruz Biotechnology) together with Amersham ECL (Amersham Biosciences, UK) were used to detect immunoreactive proteins.…”