Takeshi Yamamoto

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^hi memory-type Th2 cells are identified as a pathogenic subpopulation in eosinophilic airway inflammation. These ST2^hi 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⁺ 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