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Abstract The altered homeostasis of mitochondria-associated endoplasmic reticulum (ER) membranes (MAM) was closely associated with the pathological process of nervous system diseases and insulin resistance. Here, the exact implication of phosphofurin acidic cluster sorting protein 2 (PCAS-2), an anchor protein in the MAM interface, in diabetic kidney disease was investigated. In the kidneys of type 1 and type 2 diabetes mice and HG-induced HK-2 cells, a notable disruption of ER-mitochondria interactions, accompanied by a decreased PACS-2 expression in all subcellular fractions. Furthermore, PACS-2 knockout mice with diabetes displayed accelerated development of proteinuria, deterioration of kidney function, and aggravated disruption of MAM area, ER stress, mitochondrial dysfunction, renal apoptosis, and fibrosis. However, overexpression of PACS-2 effectively protected diabetic kidneys and HG-treated HK-2 cells from renal tubular impairments. Importantly, experimental uncoupling of ER-mitochondria contacts reversed the protective effects of PACS-2 restoration on HK-2 cells under HG conditions. In summary, our data indicate a pivotal role of PACS-2 in the development of diabetic renal tubular injury via the stabilization of MAM.

High oleic acid peanut (HOAP) is extensively embraced in China because of its high nutritional value and enhanced oxidative stability. However, its dissemination has been severely constrained in high altitude and high latitude areas due to chilling stress during sowing, resulting in significant yield loss in these regions. Despite the lack of understanding of the molecular mechanisms underlying low temperature germination (LTG) in HOAP, discovering the quantitative trait loci (QTL) that confer this trait will undoubtedly benefit breeding efforts. In the present study, we identified putative genomic regions and single nucleotide polymorphisms (SNPs) that govern LTG tolerance of HOAP in an F2 population derived from the cross of chilling-tolerant YH65 and chilling-sensitive FL14 using bulk segregant analysis (BSA). Analysis of ΔSNP-index and Euclidean distance (ED) value association pinpointed the overlapped region to a 2.29 Mb interval on chromosome A05. The candidate interval showed that 122 genes were significantly related to response to abiotic stress and plant–pathogen interaction. Furthermore, an SNP site associated with LTG tolerance was discovered. The SNP site was employed as a Kompetitive Allele Specific PCR (KASP) marker and validated in a universal peanut panel. These findings may provide valuable insight into the molecular mechanism underpinning LTG tolerance and facilitate marker-assisted selective breeding in HOAP.

Growth arrest and DNA damage-inducible beta (GADD45B) is closely linked with cell cycle arrest, DNA repair, cell survival, or apoptosis in response to stress and is known to regulate the mitogen-activated protein kinase (MAPK) pathway. Here, using an RNA sequencing approach, we determined that GADD45B was significantly upregulated in diabetic kidneys, which was accompanied by renal tubular epithelial-mesenchymal transition (EMT) and apoptosis, as well as elevated MAPK pathway activation. In vitro, GADD45B expression in cultured human kidney proximal tubular epithelial cells (HK-2 cells) was also stimulated by high glucose (HG). In addition, overexpression of GADD45B in HK-2 cells exacerbated renal tubular EMT and apoptosis and increased p38 MAPK and c-Jun N-terminal kinases (JNK) activation, whereas knockdown of GADD45B reversed these changes. Notably, the activity of extracellular regulated kinase (ERK) was not affected by GADD45B expression. Furthermore, inhibitors of p38 MAPK (SB203580) and JNK (SP600125) alleviated HG‐ and GADD45B overexpression-induced renal tubular epithelial-mesenchymal transition and apoptosis. These findings indicate a role of GADD45B in diabetes-induced renal tubular EMT and apoptosis via the p38 MAPK and JNK pathways, which may be an important mechanism of diabetic kidney injury.