Role of cyclooxygenase-2-mediated prostaglandin E2-prostaglandin E receptor 4 signaling in cardiac reprogramming

Direct cardiac reprogramming from fibroblasts can be a promising approach for disease modeling, drug screening, and cardiac regeneration in pediatric and adult patients. However, postnatal and adult fibroblasts are less efficient for reprogramming compared with embryonic fibroblasts, and barriers to cardiac reprogramming associated with aging remain undetermined. In this study, we screened 8400 chemical compounds and found that diclofenac sodium (diclofenac), a non-steroidal anti-inflammatory drug, greatly enhanced cardiac reprogramming in combination with Gata4, Mef2c, and Tbx5 (GMT) or GMT plus Hand2. Intriguingly, diclofenac promoted cardiac reprogramming in mouse postnatal and adult tail-tip fibroblasts (TTFs), but not in mouse embryonic fibroblasts (MEFs). Mechanistically, diclofenac enhanced cardiac reprogramming by inhibiting cyclooxygenase-2, prostaglandin E2/prostaglandin E receptor 4, cyclic AMP/protein kinase A, and interleukin 1β signaling and by silencing inflammatory and fibroblast programs, which were activated in postnatal and adult TTFs. Thus, anti-inflammation represents a new target for cardiac reprogramming associated with aging

低用量アスピリンによる十二指腸輪状潰瘍の一例

京都府立医科大学附属北部医療センター　消化器内科京都府立医科大学消化器内科学Department of Gastroenterology and Hepatology, North Medical Center, Kyoto Prefectural University of MedicineDepartment of Gastroenterology and Hepatology, Kyoto Prefectural University of Medicine症例は74歳男性。主訴は腹痛と嘔吐。造影CTにて十二指腸下行脚の壁肥厚と狭窄を認め、上部消化管内視鏡検査では同部位に輪状潰瘍及び高度狭窄を認めた。冠動脈疾患と脳梗塞の既往から低用量アスピリン(LDA)を内服していたためLDA潰瘍と診断した。薬物治療としてボノプラザンの投与を開始し、十二指腸狭窄に対してバルーン拡張術を施行したところ、輪状潰瘍は治癒し現在も再発を認めていない。(著者抄録