心不全や心筋梗塞などの循環器疾患の他、腎臓病、糖尿病や肺線維症などのオステオポンチン(OPN)が関与する病態解明研究を実施した。Spp1-EGFP Knock-in reporter マウスを用いた心筋梗塞、大動脈弁狭窄症、肥満、片腎動脈結紮腎線維化及び肺線維化モデルでは、それぞれ臓器特異的なOPN産生細胞が出現して病態を増悪させることを明らかにした。大動脈弁狭窄症の大動脈弁、心筋梗塞後の心臓、肥満患者の内臓脂肪、慢性腎不全の腎臓、肺線維症の肺など生活習慣病に関連する多臓器の単細胞遺伝子発現解析のデータの細胞間相互作用解析を実施してOPNシグナルによる病態増悪機序を解明した。
We conducted pathophysiological research involving osteopontin (OPN), which is associated with heart diseases such as heart failure and myocardial infarction, as well as kidney disease, diabetes, and pulmonary fibrosis. Using Spp1-EGFP Knock-in reporter mice, I elucidated that organ-specific OPN-producing cells appeared in models of myocardial infarction, aortic valve stenosis, obesity, renal fibrosis after unilateral renal artery ligation, and pulmonary fibrosis, exacerbating the respective pathologies. The cell-cell interaction analysis of single-cell RNA-seq data from multiple organs related to lifestyle diseases such as aortic valve stenosis, post-infarcted heart, visceral fat of obese patients, kidneys of chronic kidney disease patients, and lungs of pulmonary fibrosis patients, I clarified the pathogenic exacerbation mechanisms via OPN signaling.
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