Secreted Frizzled-related protein 1 regulates the progression of renal fibrosis in a mouse model of obstructive nephropathy

Renal fibrosis is responsible for progressive renal diseases that cause chronic renal failure. Secreted Frizzled-related protein 1 (Sfrp1) is highly expressed in kidney, although little is known about connection between the protein and renal diseases. Here we focused on Sfrp1 to investigate its roles in renal fibrosis using a mouse model of unilateral ureteral obstruction (UUO). In wild-type mice, the expression of Sfrp1 protein was markedly increased after UUO. The kidneys from Sfrp1 knockout mice showed significant increase in expression of myofibrobast markers, alpha-smooth muscle actin (SMA). Sfrp1 deficiency also increased protein levels of the fibroblast genes, Vimentin, and decreased those of the epithelial genes, E-cadherin, indicated that enhanced epithelial-to-mesenchymal transition (EMT). There was no difference in the levels of canonical Wnt signaling; rather the levels of phosphorylated c-Jun and JNK were more increased in the Sfrp1-/- obstructed kidney. Moreover, the apoptotic cell population was significantly elevated in the obstructed kidneys from Sfrp1-/- mice following UUO, but was slightly increased in those from wild-type mice. These results indicate that Sfrp1 is required for inhibition of renal damage through non-canonical Wnt/PCP pathway

Structural stability and aromaticity of pristine and doped graphene nanoflakes

We have quantitatively investigated the relationship between the aromaticity and structural stability of graphene nanoflakes (GNFs) using first-principles calculations. The aromaticity of each six-membered ring of GNFs is evaluated with the nucleus-independent chemical shifts (NICS). We have found that for armchair-edge GNFs, the degree of stability, that is, the edge formation energy, is proportional to the average NICS for all six-membered rings. Even for nitrogen- and boron-doped GNFs, the average NICS strongly correlates with the doping formation energy. Our results indicate that NICS is a good measure not only for the aromaticity but also for the structural stability of pristine/doped nanographene systems

鶏肉腫白血病ウイルスの宿主特異性に基づいた多経路選択的遺伝子 導入法の開発

学位の種別: 課程博士審査委員会委員 : (主査)東京大学教授 上田 泰己, 東京大学教授 尾藤 晴彦, 東京大学教授 廣瀬 謙造, 東京大学教授 饗場 篤, 東京大学講師 山口 正洋University of Tokyo(東京大学

Feedback Control of the Arachidonate Cascade in Osteoblastic Cells by 15-deoxy-Δ12,14-Prostaglandin J2

15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and an anti-diabetic thiazolidinedione, troglitazone (TRO) are peroxisome proliferator-activated receptor (PPAR)-γ ligands, which regulate immuno-inflammatory reactions as well as adipocyte differentiation. We previously reported that 15d-PGJ2 can suppress interleukin (IL)-1β-induced prostaglandin E2 (PGE2) synthesis in synoviocytes of rheumatoid arthritis (RA). IL-1 also stimulates PGE2 synthesis in osteoblasts by regulation of cyclooxygenase (COX)-2 and regulates osteoclastic bone resorption in various diseases such as RA and osteoporosis. In this study, we investigated the feedback mechanism of the arachidonate cascade in mouse osteoblastic cells, MC3T3-E1 cells, which differentiate into mature osteoblasts. Treatment with 15d-PGJ2 led to a significant increase in IL-1α-induced COX-2 expression and PGE2 production in a dose dependent manner. The effect of 15d-PGJ2 was stronger than that of TRO. However, it did not affect the expression of COX-1. In addition, cell viability of MC3T3-E1 cells was not changed in the condition we established. This means that 15d-PGJ2 exerts a positive feedback regulation of the arachidonate cascade of PGE2 in osteoblastic cells. These results may provide important information about the pathogenesis and treatment of bone resorption in a variety of diseases such as RA and osteoporosis