Project description:Isoproterenol, a β-adrenergic agonist, has been shown to induce salivary gland hyperplasia. To gain a better understanding of the underlying molecular changes altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 minutes after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. The regulation of up- and down-expression of genes related to cell proliferation/survival provides a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement.
Project description:Isoproterenol, a β-adrenergic agonist, has been shown to induce salivary gland hyperplasia. To gain a better understanding of the underlying molecular changes altered by isoproterenol, microarray-based gene expression analysis was conducted on rat parotid glands at 10, 30, and 60 minutes after isoproterenol injection. After isoproterenol treatment, the number of differentially expressed genes was increased in a time-dependent manner. The regulation of up- and down-expression of genes related to cell proliferation/survival provides a better understanding of the mechanism of isoproterenol-induced parotid gland enlargement. For the time-course experiments, male Sprague-Dawley rats (2-3 months old) were injected intra-peritoneally with isoproterenol (20 mg/g body weight) or normal saline (control). The rats were euthanized at the indicated times and the harvested parotid glands stored at -80C until analyzed. Cells were harvested and processed at the following times: control (saline), immediately after treatment (10 min) and at 30 and 60min after treatment.
Project description:Human salivary gland organoids have opened tremendous possibilities for regenerative medicine in patients undergoing radiotherapy for the treatment of head and neck cancer. However, their clinical translation is greatly limited by the current use of Matrigel for organoid derivation and expansion. Here, we envisage that the use of a fully, synthetic hydrogel based on the oligo(-ethylene glycol) functionalized polymer polyisocyanopeptides (PICs) can provide an environment suitable for the generation and expansion of salivary gland organoids (SGOs) after optimization of PIC polymer properties. We demonstrate that PIC hydrogels decorated with the cell-binding peptide RGD allow SGO formation from salivary gland (SG)-derived stem cells. This self-renewal potential is preserved for only 4 passages. It was found that SGOs differentiated prematurely in PIC hydrogels affecting their self-renewal capacity. Similarly, SGOs show decreased expression of immediate early genes (IEGs) after culture in PIC hydrogels. Activation of multiple signalling pathways involved in IEG expression by β-adrenergic agonist isoproterenol, led to increased stem cell self-renewal capacity as measured by organoid forming efficiency (OFE). These results indicate that PIC hydrogels are promising 3D matrices for SGOs, with the option to be used clinically, after further optimization of the hydrogel and culture conditions.
Project description:Inflammation is a key component of pathological angiogenesis. Here we induce cornea neovascularisation using sutures placed into the cornea, and sutures are removed to induce a regression phase. We used whole transcriptome microarray to monitor gene expression profies of several genes
Project description:Ionizing radiation (IR) – induced salivary gland damage is a common adverse effect in radiotherapy for patients with head and neck cancers. Currently, there is no effective treatment for the resulting salivary gland hypofunction and xerostomia (dry mouth). Here we profiled the acute gene expression change in the mouse submandibular salivary gland, and defined its damage response patterns at the transcriptome level.