The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease

Takata, Tomoaki; Isomoto, Hajime

doi:10.2169/internalmedicine.1342-22

Cited by 9 publications

(4 citation statements)

References 81 publications

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“…Genome-wide association studies (GWAS) have revealed the existence of variants in the UMOD gene encoding uromodulins that are susceptible to renal function, and hypertension ( 89 ), and that non-coding UMOD gene variants induce salt-sensitive hypertension and renal injury through increased expression of uromodulins ( 55 ). The relevance of urinary regulators and their role in the regulation of sodium homeostasis is consistent with the results of the human GWAS ( 90 ). Single nucleotide polymorphisms in the UMOD gene were associated with hypertension, and conversely, variants with lower UMOD levels were associated with a lower risk of hypertension ( 91 ).…”

Section: Relationship Between Uromodulin and Various Cardiovascular D...supporting

confidence: 82%

The role of uromodulin in cardiovascular disease: a review

Chen,

Zhong,

Zheng

et al. 2024

Front. Cardiovasc. Med.

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Uromodulin, also referred to as Tamm Horsfall protein (THP), is a renal protein exclusively synthesized by the kidneys and represents the predominant urinary protein under normal physiological conditions. It assumes a pivotal role within the renal system, contributing not only to ion transport and immune modulation but also serving as a critical factor in the prevention of urinary tract infections and kidney stone formation. Emerging evidence indicates that uromodulin may serve as a potential biomarker extending beyond renal function. Recent clinical investigations and Mendelian randomization studies have unveiled a discernible association between urinary regulatory protein levels and cardiovascular events and mortality. This review primarily delineates the intricate relationship between uromodulin and cardiovascular disease, elucidates its predictive utility as a novel biomarker for cardiovascular events, and delves into its involvement in various physiological and pathophysiological facets of the cardiovascular system, incorporating recent advancements in corresponding genetics.

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Section: Relationship Between Uromodulin and Various Cardiovascular D...supporting

confidence: 82%

The role of uromodulin in cardiovascular disease: a review

Chen,

Zhong,

Zheng

et al. 2024

Front. Cardiovasc. Med.

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“…AGTR1 [85] and UMOD (uromodulin) [86] expression is a potential target for diabetic nephropathy. AGTR1 [87] and UMOD (uromodulin) [88] play an important role in chronic kidney disease. UMOD (uromodulin) [89] was observed to be associated with the risk of kidney fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Vastrad,

Vastrad

2024

Preprint

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Acute kidney injury (AKI) is a type of renal disease occurs frequently in hospitalized patients, which may cause abnormal renal function and structure with increase in serum creatinine level with or without reduced urine output. With the incidence of AKI is increasing. However, the molecular mechanisms of AKI have not been elucidated. It is significant to further explore the molecular mechanisms of AKI. We downloaded the GSE139061 next generation sequencing (NGS) dataset from the Gene Expression Omnibus (GEO) database. Limma R bioconductor package was used to screen the differentially expressed genes (DEGs). Then, the enrichment analysis of DEGs in Gene Ontology (GO) function and REACTOME pathways was analyzed by g:Profiler. Next, the protein-protein interaction (PPI) network and modules was constructed and analyzed, and the hub genes were identified. Next, the miRNA-hub gene regulatory network and TF-hub gene regulatory network were built. We also validated the identified hub genes via receiver operating characteristic (ROC) curve analysis. Overall, 956 DEGs were identified, including 478 up regulated and 478 down regulated genes. The enrichment functions and pathways of DEGs involve primary metabolic process, small molecule metabolic process, striated muscle contraction and metabolism. Topological analysis of the PPI network and module revealed that hub genes, including PPP1CC, RPS2, MDFI, BMI1, RPL23A, VCAM1, ALB, SNCA, DPP4 and RPL26L1, might be involved in the development of AKI. miRNA-hub gene and TF-hub gene regulatory networks revealed that miRNAs and TFs including hsa-mir-510-3p, hsa-mir-6086 and mir-146a-5p, MAX and PAX2, might be involved in the development of AKI. Various known and newtherapeutic targets were obtained via network analysis. The results of the current investigation might be beneficial for the diagnosis and treatment of AKI.

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“…PA-induced ER stress has been demonstrated in hepatocytes and cardiomyocytes [ 27 , 28 ]. In the kidney, ER stress is a significant contributor to acute and chronic renal injury of various etiologies [ 29 , 30 ]; thus, it could be a therapeutic target for steatonephropathy. We previously reported, in high-fat diet-fed mice, that ectopic lipid accumulation in the renal tubule causes ER stress and interstitial fibrosis.…”

Section: Discussionmentioning

confidence: 99%

Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules

Hamada

Mae

Takata

et al. 2023

IJMS

Self Cite

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Steatosis, or ectopic lipid deposition, is the fundamental pathophysiology of non-alcoholic steatohepatitis and chronic kidney disease. Steatosis in the renal tubule causes endoplasmic reticulum (ER) stress, leading to kidney injury. Thus, ER stress could be a therapeutic target in steatonephropathy. Five-aminolevulinic acid (5-ALA) is a natural product that induces heme oxygenase (HO)-1, which acts as an antioxidant. This study aimed to investigate the therapeutic potential of 5-ALA in lipotoxicity-induced ER stress in human primary renal proximal tubule epithelial cells. Cells were stimulated with palmitic acid (PA) to induce ER stress. Cellular apoptotic signals and expression of genes involved in the ER stress cascade and heme biosynthesis pathway were analyzed. The expression of glucose-regulated protein 78 (GRP78), a master regulator of ER stress, increased significantly, followed by increased cellular apoptosis. Administration of 5-ALA induced a remarkable increase in HO-1 expression, thus ameliorating PA-induced GRP78 expression and apoptotic signals. BTB and CNC homology 1 (BACH1), a transcriptional repressor of HO-1, was significantly downregulated by 5-ALA treatment. HO-1 induction attenuates PA-induced renal tubular injury by suppressing ER stress. This study demonstrates the therapeutic potential of 5-ALA against lipotoxicity through redox pathway.

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The Versatile Role of Uromodulin in Renal Homeostasis and Its Relevance in Chronic Kidney Disease

Cited by 9 publications

References 81 publications

The role of uromodulin in cardiovascular disease: a review

The role of uromodulin in cardiovascular disease: a review

Identification of novel prognostic targets in acute kidney injury using bioinformatics and next generation sequencing data analysis

Five-Aminolevulinic Acid (5-ALA) Induces Heme Oxygenase-1 and Ameliorates Palmitic Acid-Induced Endoplasmic Reticulum Stress in Renal Tubules

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