The University of Osaka · 의학
타케시 야마모토 교수의 연구실은 대사성 질환, 특히 비만과 관련된 만성 신장질환에서의 지질독성(lipotoxicity)과 자가분해작용(autophagy)의 역할을 중심으로 연구를 진행하고 있습니다. 신장 근치세포에서의 리소좀 기능 이상과 자가분해 경로의 손상이 지방 축적과 세포 손상으로 이어지는 메커니즘을 규명하며, 특히 TFEB 전사인자와 오메가-3 지방산(EPA)이 이 과정을 조절하는 데 기여함을 밝혀내었습니다. 또한, 자가분해 작용의 조절 메커니즘과 면역세포의 병태생리학적 기여를 통해 만성 염증 및 신장 손상의 새로운 치료 타겟을 모색하고 있습니다.
표시된 성과는 수집된 데이터 기준으로 산출되며, 일부 차이가 있을 수 있습니다.
Excessive fat intake contributes to the progression of metabolic diseases <i>via</i> cellular injury and inflammation, a process termed lipotoxicity. Here, we investigated the role of lysosomal dysfunction and impaired autophagic flux in the pathogenesis of lipotoxicity in the kidney. In mice, a high-fat diet (HFD) resulted in an accumulation of phospholipids in enlarged lysosomes within kidney proximal tubular cells (PTCs). In isolated PTCs treated with palmitic acid, autophagic degradation act
Autophagy plays an essential role in cellular homeostasis through the quality control of proteins and organelles. Although a time-dependent decline in autophagic activity is believed to be involved in the aging process, the issue remains controversial. We previously demonstrated that autophagy maintains proximal tubular cell homeostasis and protects against kidney injury. Here, we extend that study and examine how autophagy is involved in kidney aging. Unexpectedly, the basal autophagic activity
Recently, we identified a novel mechanism of lipotoxicity in the kidney proximal tubular cells (PTECs); lipid overload stimulates macroautophagy/autophagy for the renovation of plasma and organelle membranes to maintain the integrity of the PTECs. However, this autophagic activation places a burden on the lysosomal system, leading to a downstream suppression of autophagy, which manifests as phospholipid accumulation and inadequate acidification in lysosomes. Here, we investigated whether pharmac
The complete nucleotide sequence of one of the immediate-early genes of human herpesvirus 6 variant B was determined and compared with that of variant A reported by Martin et al. (M.D. Martin, J. Nicholas, B. J. Thomson, C. Newman, and R. W. Honess, J. Virol. 65:5381-5390, 1991). While it was reported that two open reading frames exist in this region of variant A, only one open reading frame was found in variant B and the putative coding region of variant B was 2,679 nucleotides long. Furthermor
Obesity is a major risk factor for end-stage kidney disease. We previously found that lysosomal dysfunction and impaired autophagic flux contribute to lipotoxicity in obesity-related kidney disease, in both humans and experimental animal models. However, the regulatory factors involved in countering renal lipotoxicity are largely unknown. Here, we found that palmitic acid strongly promoted dephosphorylation and nuclear translocation of transcription factor EB (TFEB) by inhibiting the mechanistic
ST2<sup>hi</sup> memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2<sup>hi</sup> pathogenic Th2 cells produce large amount of IL-5 upon T cell receptor stimulation, but not in response to IL-33 treatment. By contrast, IL-33 alone induces cytokine production in ST2<sup>+</sup> group 2 innate lymphoid cells (ILC2). Here we show that a MAPK phosphatase Dusp10 is a key negative regulator of IL-33-induced cytokine production in Th2 cells.
The renoprotective effects of SLC5A2/SGLT2 (solute carrier 5 (sodium/glucose cotransporter), member 2) inhibitors have recently been demonstrated in non-diabetic chronic kidney disease (CKD), even without overt albuminuria. However, the mechanism underlying this renoprotection is largely unclear. We investigated the renoprotective mechanisms of the SLC5A2 inhibitor empagliflozin with a focus on ALB (albumin) reabsorption and macroautophagy/autophagy in proximal tubules using wild-type or drug-in
A feasibility study has been conducted to determine whether mathematical models can be used for the numerical simulation of metal active gas (MAG) arc welding. In the present work, a three-dimensional, nonstationary thermal model for fillet welding is developed. The transient temperature distribution in the base metal is numerically analysed to estimate the molten pool size using a finite difference model based on the heat flow equation, and the theoretical configuration of the molten pool is ca
The idea of enabling the capacity of a compressor motor to be varied might have originally been aimed at changing the compressor capacity irrespective of energy saving. That is why the following points might have been given priority over other merits: Improving reliability of the compressor, which is lowered by frequent ON/OFF operations; Preventing the durability of magnet switch (starter) from lowering because of ON/OFF operations; Improving comfort by reducing the width of fluctuation in the
