Calcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion, OPN, KIM-1, and ERK expression

Li, Xiaoran; Chen, Siyu; Feng, Demei; Fu, Yuqiang; Wu, Huayue; Lü, Jing; Bao, Jiguang

doi:10.1080/0886022x.2021.1881554

Cited by 12 publications

(6 citation statements)

References 43 publications

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“…Experimental and clinical evidence has established that oxidative stress plays an important role in cytokine/chemokine secretions and podocyte/mesangial cell injury, leading to glomerular fibrosis and kidney failure. 26 , 27 Our present findings demonstrated that the 5/6Nx-injured kidney tissues with and without chronic stress had increased levels of p22 Phox and gp91 Phox genes and proteins, as well as oxidative stress production. p22 Phox and gp91 Phox are important membrane-type subunits of NADPH oxidase.…”

Section: Discussionsupporting

confidence: 55%

Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress

et al. 2022

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Background: Chronic psychological stress is a risk factor for kidney disease, including kidney dysfunction and hypertension. Lysosomal CatK (cathepsin K) participates in various human pathobiologies. We investigated the role of CatK in kidney remodeling and hypertension in response to 5/6 nephrectomy injury in mice with or without chronic stress. Methods: Male 7-week-old WT (wild type; CatK +/+ ) and CatK-deficient (CatK −/− ) mice that were or were not subjected to chronic stress underwent 5/6 nephrectomy. At 8 weeks post-stress/surgery, the stress was observed to have accelerated injury-induced glomerulosclerosis, proteinuria, and blood pressure elevation. Results: Compared with the nonstressed mice, the stressed mice showed increased levels of TLR (Toll-like receptor)-2/4, p22 phox , gp91 phox , CatK, MMP (matrix metalloproteinase)-2/9, collagen type I and III genes, PPAR-γ (peroxisome proliferator-activated receptor-gamma), NLRP-3 (NOD-like receptor thermal protein domain associated protein 3), p21, p16, and cleaved caspase-8 proteins, podocyte foot process effacement, macrophage accumulation, apoptosis, and decreased levels of Bcl-2 (B cell lymphoma 2) and Sirt1, as well as decreased glomerular desmin expression in the kidneys. These harmful changes were retarded by the genetic or pharmacological inhibition of CatK. Consistently, CatK inhibition ameliorated 5/6 nephrectomy–related kidney injury and dysfunction. In mesangial cells, CatK silencing or overexpression, respectively, reduced or increased the PPAR-γ and cleaved caspase-8 protein levels, providing evidence and a mechanistic explanation of CatK’s involvement in PPAR-γ/caspase-8–mediated cell apoptosis in response to superoxide and stressed serum. Conclusions: These results demonstrate that CatK plays an essential role in kidney remodeling and hypertension in response to 5/6 nephrectomy or stress, possibly via a reduction of glomerular inflammation, apoptosis, and fibrosis, suggesting a novel therapeutic strategy for controlling kidney injury in mice under chronic psychological stress conditions.

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Section: Discussionsupporting

confidence: 55%

Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress

et al. 2022

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“…Calcium-sensing receptors (CaSR) were involved in the induction of kidney calculi related proteins. Calculi related proteins and ERK were upregulated in the kidney of rats treated with Calcium oxalate and cell apoptosis may lead to crystal adhesion on the surface of kidney cells to form calculi [24] . MicroRNAs (miRNAs) are important regulatory factors of gene expression, which play a key role in the occurrence and development of tumors and can also regulate ERK signal, which is usually overexpressed in cancerous tissues.…”

Section: Discussionmentioning

confidence: 99%

Seasonal expression of extracellular signal regulated kinases in the colon of wild ground squirrels (Spermophilus dauricus)

et al. 2022

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Background: The aim of this study was to explore the localization and expression of extracellular signal regulated kinase/phospho-extracellular signal regulated kinases (ERK/pERK) in the colonic tissue of wild ground squirrels (Spermophilus dauricus) in the breeding season and the non-breeding season.Methods and Results: Hematoxylin-eosin staining, immunohistochemistry, real-time quantitative PCR and Western blot were used in this study. The histological results showed that the diameter of the colon lumen in the non-breeding season was larger than that in the breeding season, and the number of glandular cells in the non-breeding season was also more than those in the breeding season. The immunochemical results showed that ERK1/2 was expressed in the cytoplasm of goblet cells and intestinal epithelial cells, while pERK1/2 was expressed in the cytoplasm and nucleus of goblet cells and intestinal epithelial cells. The immunolocalization of ERK1/2 and pERK1/2 expression were more obvious in the non-breeding season, especially in intestinal epithelial cells. The results of real-time quantitative PCR and Western blot showed that the expression of ERK1/2 and pERK1/2 in the breeding season was signi cantly lower than that in the non-breeding season.Conclusions: The expression of ERK1/2 and pERK1/2 in the colons of the wild ground squirrels had seasonal changes, which had signi cant increases in the non-breeding season comparing to those in the breeding season. This study revealed the potential role of ERK1/2 in colon to the adaptation of seasonal changes in wild ground squirrel.

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“…Increased urinary excretion of calcium ions is an important factor in the formation of calcium stones [24,33]. The calcium-sensing receptor (CaSR) plays a role in inhibiting calcium reabsorption and promoting the precipitation of CaP and oxalate when stimulated by elevated serum calcium levels [34,35]. Three claudin genes, namely claudin-14, claudin-16, and claudin-19, are involved in calcium ion transport in the thick ascending limb of Henle and have been linked to renal diseases, such as hypercalciuria, kidney stones, and bone mineral loss.…”

Section: Regulation Of Calcium Metabolismmentioning

confidence: 99%

Non-Coding RNAs in Kidney Stones

Wang,

Mi,

Bai

et al. 2024

Biomolecules

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Nephrolithiasis is a major public health concern associated with high morbidity and recurrence. Despite decades of research, the pathogenesis of nephrolithiasis remains incompletely understood, and effective prevention is lacking. An increasing body of evidence suggests that non-coding RNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), play a role in stone formation and stone-related kidney injury. MiRNAs have been studied quite extensively in nephrolithiasis, and a plethora of specific miRNAs have been implicated in the pathogenesis of nephrolithiasis, involving remarkable changes in calcium metabolism, oxalate metabolism, oxidative stress, cell–crystal adhesion, cellular autophagy, apoptosis, and macrophage (Mp) polarization and metabolism. Emerging evidence suggests a potential for miRNAs as novel diagnostic biomarkers of nephrolithiasis. LncRNAs act as competing endogenous RNAs (ceRNAs) to bind miRNAs, thereby modulating mRNA expression to participate in the regulation of physiological mechanisms in kidney stones. Small interfering RNAs (siRNAs) may provide a novel approach to kidney stone prevention and treatment by treating related metabolic conditions that cause kidney stones. Further investigation into these non-coding RNAs will generate novel insights into the mechanisms of renal stone formation and stone-related renal injury and might lead to new strategies for diagnosing and treating this disease.

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Calcium-sensing receptor promotes calcium oxalate crystal adhesion and renal injury in Wistar rats by promoting ROS production and subsequent regulation of PS ectropion, OPN, KIM-1, and ERK expression

Cited by 12 publications

References 43 publications

Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress

Cathepsin K Deficiency Prevented Kidney Damage and Dysfunction in Response to 5/6 Nephrectomy Injury in Mice With or Without Chronic Stress

Seasonal expression of extracellular signal regulated kinases in the colon of wild ground squirrels (Spermophilus dauricus)

Non-Coding RNAs in Kidney Stones

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