Project description:Histone deacetylase (HDAC) inibitors suppress cell proliferation of prostate cancer, but the detailed mechanisms are unknown. Moreover, HDAC includes 18 family members, namely HDAC1-11 and SIRT1-7, and differences of effects on prostate cancer proliferation among these enzymes are also unknown. Thus, we clarified differences of gene expression between prostate cancer cell line (LNCaP) treated with pan-HDAC inhibitors (TSA and OBP-801) or selective HDAC inhibitor (NCC-149, HDAC8-specific inhibitor)using cDNA microarray. LNCaP treated with TSA (1μM), NCC149 (2μM), OBP-801 (200nM) or DMSO for 24hrs, RNA was extracted from cells, and cDNA array was performed.
Project description:Histone deacetylase (HDAC) inibitors suppress cell proliferation of prostate cancer, but the detailed mechanisms are unknown. Moreover, HDAC includes 18 family members, namely HDAC1-11 and SIRT1-7, and differences of effects on prostate cancer proliferation among these enzymes are also unknown. Thus, we clarified differences of gene expression between prostate cancer cell line (LNCaP) treated with pan-HDAC inhibitors (TSA and OBP-801) or selective HDAC inhibitor (NCC-149, HDAC8-specific inhibitor)using cDNA microarray.
Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.
Project description:miRNA expression was obtained from non-treated or OBP-801 treated TRAP rats which develop prostate cancer. The primary aim was to identify miRNAs which regulate prostate carcinogenesis induced by OBP-801.
Project description:In order to establish a rat embryonic stem cell transcriptome, mRNA from rESC cell line DAc8, the first male germline competent rat ESC line to be described and the first to be used to generate a knockout rat model was characterized using RNA sequencing (RNA-seq) analysis.
