Periostin Associates with Notch1 Precursor to Maintain Notch1 Expression under a Stress Condition in Mouse Cells

Abstract

BackgroundMatricellular proteins, including periostin, modulate cell-matrix interactions and cell functions by acting outside of cells.Methods and FindingsIn this study, however, we reported that periostin physically associates with the Notch1 precursor at its EGF repeats in the inside of cells. Moreover, by using the periodontal ligament of molar from periostin-deficient adult mice (Pn−/− molar PDL), which is a constitutively mechanically stressed tissue, we found that periostin maintained the site-1 cleaved 120-kDa transmembrane domain of Notch1 (N1™) level without regulating Notch1 mRNA expression. N1™ maintenance in vitro was also observed under such a stress condition as heat and H2O2 treatment in periostin overexpressed cells. Furthermore, we found that the expression of a downstream effector of Notch signaling, Bcl-xL was decreased in the Pn−/− molar PDL, and in the molar movement, cell death was enhanced in the pressure side of Pn−/− molar PDL.ConclusionThese results suggest the possibility that periostin inhibits cell death through up-regulation of Bcl-xL expression by maintaining the Notch1 protein level under the stress condition, which is caused by its physical association with the Notch1 precursor.

The multiple facets of periostin in bone metabolism

“…These data suggest that mechanical strain will activate latent TGF-β and twist-1 nuclear translocation, resulting in periostin activation. Finally, periostin null mice submitted to experimental tooth movement showed an increased PDL cells death associated with a reduced expression of Notch-1 and its downstream effector Bcl-xl, known to play an important role in cell survival under stress condition [67,68]. These results suggest that periostin associates with Notch-1 to maintain its expression and subsequent signaling in order to enhance cell tolerance against the stress and protect them from death [68].…”

“…In summary, these data show that periostin is a prosurvival protein, largely involved in cell response to environmental stress [61,63,68]. By binding to integrins or cell surface receptors, periostin can activate intracellular signaling pathways leading to inhibition of apoptosis through inactivation of caspases 3 and 9 and prosurvival signaling resulting in increased bone formation [12,61,66,73].…”

“…Notch proteins are transmembrane receptors that affect osteoblast differentiation and play important roles in anti-cell death function under mechanical stress [52]. A reduced expression of Notch1 and its downstream effector Bcl-xl has been described in PDL and femur of periostin null mice compared to normal mice [56,68,69]. By binding to Notch, periostin up-regulates expression of Notch and Bcl-xl, leading to inhibition of cell death, especially in stress conditions.…”

Role and underlying mechanisms of the interstitial protein periostin in the diagnosis and treatment of malignant tumors (Review)

“…involved in numerous normal physiological processes, but are also closely associated with the pathological processes involved in the occurrence and development of cardiovascular diseases, asthma and tumors (16). Currently, the majority of studies indicate that the overexpression of periostin is associated with the malignancy grade of a cancer; however, other studies have reported that periostin may inhibit the invasion and metastasis of bladder cancer (17,18).…”

Periostin in dental science

“…The EMI domain, which is a small module rich in cysteine residues found in members of the EMILIN family, is a site for protein-protein interaction [11]. Periostin directly interacts with type I collagen [12][13][14], fibronectin [15], and Notch1 [16] through its EMI domain, with tenascin-C [15] and BMP-1 [17] through its fas I domains, and with laminin g2 though the nature of the interaction is yet unknown [18]. These periostin interactions with mainly extracellular matrix molecules firstly occur intracellularly [15].…”