ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

Sharma, K. R.; Heckler, Karl; Stoll, Sandra J.; Hillebrands, Jan-Luuk; Kynast, Katharina L.; Herpel, Esther; Porubský, Štefan; Elger, Marlies; Hadaschik, Boris; Bieback, Karen; Hammes, Hans‐Peter; Nawroth, Peter P.; Krøll, Jens

doi:10.1038/srep37172

Cited by 39 publications

(45 citation statements)

References 33 publications

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“…They confirmed the animal data with immunohistochemical analysis of human kidneys from patients with DKD. Those authors concluded that the overexpression of the ELMO1 gene occurs due to the glomerular protection and survival of renal cells by decreasing apoptosis under hyperglycaemic conditions [19].…”

Section: Snp Genotypingmentioning

confidence: 99%

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

Kwiendacz

Nabrdalik

Adamczyk

et al. 2020

Endokrynologia Polska

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Introduction: Multifactorial pathogenesis of diabetic kidney disease (DKD) consists of a combination of metabolic, environmental, and genetic factors. A genome-wide association study has shown that ELMO1 is a candidate gene for DKD occurrence and progression. The aim of this study was to assess the association of a single nucleotide polymorphism (rs741301) of the ELMO1 gene with DKD in Polish patients with type 2 diabetes (T2DM). Material and methods: This was a case/control study of 272 T2DM patients with or without DKD. Patients were divided into groups depending on DKD definition according to the American Diabetes Association (ADA) and the National Kidney Foundation (NKF). The association of the rs741301 polymorphism with DKD was assessed in the whole study group as well as in the subgroups stratified according to the presence of DKD. Results: There was no association between rs741301 polymorphisms and the presence of DKD in relation to the ADA definition (p = 0.6) or the NKF definition (p = 0.5) of DKD and with estimated glomelural filtration rate (eGFR) value reflecting the stage of the chronic kidney disease (p = 0.8). Conclusions: Even though the results of this study are negative, there is still a great need for larger studies assessing the genetic susceptibility to DKD to identify patients who are particularly prone to this complication.

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Section: Snp Genotypingmentioning

confidence: 99%

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

Kwiendacz

Nabrdalik

Adamczyk

et al. 2020

Endokrynologia Polska

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“…ELMO1 also serves as a regulator of cyclooxygenase-2 (COX-2) activity, which aggravates glomerular injury and thus stimulates COX-2-mediated fibronectin accumulation in the development of glomerulosclerosis [51]. However, Sharma et al [52] found that ELMO1 exerts a protective effect on the kidneys in zebrafish and human samples. Their results highlighted ELMO1 as an important factor for glomerular protection and renal cell survival by decreasing apoptosis, especially under diabetic conditions.…”

Section: Inflammation and Oxidative Stress-related Genesmentioning

confidence: 99%

The Susceptibility Genes in Diabetic Nephropathy

Wei

Xiao

et al. 2018

Kidney Dis

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Background: Diabetes mellitus (DM) poses a severe threat to global public health. Diabetic nephropathy (DN) is one of the most common complications of diabetes and the leading cause of end-stage renal disease (ESRD). Approximately 30–40% of DM patients in the world progress to ESRD, which emphasizes the effect of genetic factors on DN. Family clustering also supports the important role of hereditary factors in DN and ESRD. Therefore, a large number of genetic studies have been carried out to identify susceptibility genes in different diabetic cohorts. Extensive susceptibility genes of DN and ESRD have not been identified until recently. Summary and Key Messages: Some of these associated genes function as pivotal regulators in the pathogenesis of DN, such as those related to glycometabolism and lipid metabolism. However, the functions of most of these genes remain unclear. In this article, we review several susceptibility genes according to their genetic functions to make it easier to determine their exact effect on DN and to provide a better understanding of the advancements from genetic studies. However, several challenges associated with investigating the genetic factors of DN still exist. For instance, it is difficult to determine whether these variants affect the expression of the protein they encode or other cytokines. More efforts should be made to determine how these genes influence the progression of DN. In addition, many results could not be replicated among races, suggesting that the association between genetic polymorphisms and DN is race-specific. Therefore, large, well-designed studies involving more relevant variables and ethnic groups and more relevant functional studies are urgently needed. These studies may be beneficial and retard the progression of DN by early intervention, especially for patients who carry certain risk alleles or genotypes.

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“…NCAM2 is primarily expressed in the brain, where it stimulates neurite outgrowth and facilitates dendritic and axonal compartmentalization [23]. ELMO1 protects endothelial cells from apoptosis [24] and it is also an important factor for glomerular protection and renal cell survival via decreasing apoptosis, especially under diabetic conditions [25].…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement

Łuczkowska

Rogińska

Ulańczyk

et al. 2020

IJMS

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Bortezomib is an anti-tumor agent, which inhibits 26S proteasome degrading ubiquitinated proteins. While apoptotic transcription-associated activation in response to bortezomib has been suggested, mechanisms related to its influence on post-transcriptional gene silencing mediated regulation by non-coding RNAs remain not fully elucidated. In the present study, we examined changes in global gene and miRNA expression and analyzed the identified miRNA–mRNA interactions after bortezomib exposure in human neuroblastoma cells to define pathways affected by this agent in this type of cells. Cell viability assays were performed to assess cytotoxicity of bortezomib. Global gene and miRNA expression profiles of neuroblastoma cells after 24-h incubation with bortezomib were determined using genome-wide RNA and miRNA microarray technology. Obtained results were then confirmed by qRT-PCR and Western blot. Further bioinformatical analysis was performed to identify affected biological processes and pathways. In total, 719 genes and 28 miRNAs were downregulated, and 319 genes and 61 miRNAs were upregulated in neuroblastoma cells treated with bortezomib. Possible interactions between dysregulated miRNA/mRNA, which could be linked to bortezomib-induced neurotoxicity, affect neurogenesis, cellular calcium transport, and neuron death. Bortezomib might exert toxic effects on neuroblastoma cells and regulate miRNA–mRNA interactions influencing vital cellular functions. Further studies on the role of specific miRNA–mRNA interactions are needed to elucidate mechanisms of bortezomib action.

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ELMO1 protects renal structure and ultrafiltration in kidney development and under diabetic conditions

Cited by 39 publications

References 33 publications

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

Association of single nucleotide polymorphism (rs741301) of the ELMO1 gene with diabetic kidney disease in Polish patients with type 2 diabetes: a pilot study

The Susceptibility Genes in Diabetic Nephropathy

Molecular Mechanisms of Bortezomib Action: Novel Evidence for the miRNA–mRNA Interaction Involvement

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