Highlights d cGAS-STING activation and mitochondrial damage in tubules mediate acute kidney injury d cGAS-STING activation induces tubular inflammation and progression of AKI d Mitochondrial DNA leakage into the cytosol increased in AKIinduced tubular damage d Cytosolic mitochondrial DNA activates cGAS-STING signaling in tubular inflammation

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GASDERMIN B (GSDMB) belongs to the novel gene family GASDERMIN (GSDM). All GSDM family members are located in amplicons, genomic regions often amplified during cancer development. Given that GSDMB is highly expressed in cancerous cells and the locus resides in an amplicon, GSDMB may be involved in cancer development and/or progression. However, only limited information is available on GSDMB expression in tissues, normal and cancerous, from cancer patients. Furthermore, the molecular mechanisms that regulate GSDMB expression in gastric tissues are poorly understood. We investigated the spatiotemporal expression patterns of GSDMB in gastric cancer patients and the 5' regulatory sequences upstream of GSDMB. GSDMB was not expressed in the majority of normal gastric-tissue samples, and the expression level was very low in the few normal samples with GSDMB expression. Most pre-cancer samples showed moderate GSDMB expression, and most cancerous samples showed augmented GSDMB expression. Analysis of genome sequences revealed that an Alu element resides in the 5' region upstream of GSDMB. Reporter assays using intact, deleted, and mutated Alu elements clearly showed that this Alu element positively regulates GSDMB expression and that a putative IKZF binding motif in this element is crucial to upregulate GSDMB expression.

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Organelle damage can cause various kidney diseases. In particular, organelle stress such as decreased proteostatic activity in the endoplasmic reticulum (ER) and altered energy metabolism in mitochondria contribute to glomerular and tubulointerstitial damage, resulting in the progression and development of kidney diseases. The ER regulates protein quality control via the unfolded protein response (UPR) pathway. Pathogenic ER stress leads to dysregulation of this pathway, and a maladaptive UPR is highly deleterious to renal cell function, and thereby has been implicated in the pathophysiology of various kidney diseases. The UPR pathway in the ER also regulates mitochondrial metabolic status, indicating the pathophysiological significance of organelle crosstalk between the ER and mitochondria via the UPR pathway. In recent years, it has become obvious that communication among organelles also is conducted through direct interactions at membrane contact sites (MCSs). Organelles exchange materials including lipids, ions, and proteins at the MCS. Accordingly, alterations to these networks, such as impaired ER-mitochondria MCSs, have been linked to several diseases such as neurodegeneration and diabetes. In this review, we describe the roles of organelles in kidney diseases and the mechanisms underlying organelle communication at the MCS, and especially at the mitochondria-associated ER membrane. Potential treatment options that are focused on organelle crosstalk are discussed, in addition to the relationship between this phenomenon and various diseases, especially kidney diseases.

Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD.

Three types of triple-chain surfactants bearing three sulfonate groups showed unusual behavior; that is, their critical micelle concentration measured by the Wilhelmy method for their homologous series increased with an increase in the hydrophobic alkyl chain length. Thus, the difference in the backbone structure of these surfactants, whether glycerol type (glycerol or 2-methylglycerol) or 1,1,1-tris(hydroxymethyl)ethane (i.e., trimethylolethane) type, significantly affects their surface properties. To clarify this unusual behavior, the adsorption manner of triple-chain amphiphiles bearing two or three hydroxyl groups, which are synthetic precursors of triple-chain surfactants bearing two or three anionic headgroups, was studied by measuring pressure−area (π−A) isotherms with a computer-controlled film-balance technique. Some clear-cut profiles with respect to the relationship between the structure of these amphiphiles and their adsorption behavior on the surface were revealed as follows:  (1) The packing of hydrophobic alkyl chains of triple-chain diols was tighter than that of the corresponding double-chain diols with the same alkyl chain length; (2) as to both triple-chain diols and triple-chain triols, the π−A isotherms were greatly changed depending on their backbone structure, whether glycerol, 2-methylglycerol, or trimethylolethane; (3) three additional isolated oxyethylene units connecting to the backbone of triple-chain triols contribute significantly to the increase in hydrophilicity of the molecule. These results indicate that the choice of the backbone structure of a triple-chain surfactant is important to predict and to understand the packing of hydrophobic chains, which directly relates to its surface properties in water.