Differential Gene Expression in Diabetic Nephropathy in Individuals With Type 1 Diabetes

Caramori, M. Luiza; Kim, Youngki; Goldfine, Allison B.; Moore, Jason H.; Rich, Stephen S.; Mychaleckyj, Josyf C.; Kirkpatrick, David T.; Nickerson, Helen D.; Królewski, Andrzej S.; Mauer, Michael

doi:10.1210/jc.2014-4465

Cited by 19 publications

(12 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Gene expression microarrays have been widely used in diabetic studies, because alterations in transcriptional profiles provide a robust and sensitive way to better understand the mechanisms of the disease and its complications. Microarray analyses have previously been used to investigate the mechanisms underlying diabetic cardiomyopathy [ 24 ], diabetic nephropathy [ 25 ], diabetic bone disease [ 26 ], and diabetic periodontitis [ 27 ] in diabetic patients or animal models. However, only one study has been conducted in patients with diabetic neuropathy to identify the DEGs and the related biological pathways responsible for the progression of diabetic neuropathy [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

Lin

Zhou

Cai

et al. 2017

Journal of Diabetes Research

View full text Add to dashboard Cite

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

show abstract

Section: Discussionmentioning

confidence: 99%

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

Lin

Zhou

Cai

et al. 2017

Journal of Diabetes Research

View full text Add to dashboard Cite

show abstract

“…This is further supported by the evidence of higher levels of oxidative stress in RCC patients (Hori et al, 2007;Ganesamoni et al, 2012), in renal injury related to obesity (Quigley et al, 2009), and in an experimental model of renal carcinogenesis (Gago-Dominguez et al, 2002). Increased oxidative stress and activation of oxidative stress-induced DNA damage repair pathway in kidney cells of diabetic patients have been reported (Forbes et al, 2008;Kashihara et al, 2010;Caramori et al, 2015). Additionally, several chemotherapeutic agents, including doxorubicin itself, also generate ROS and thereby increase the oxidative stress burden (Ferlini et al, 1999;Pervaiz and Clement, 2004;Sullivan and Graham, 2008).…”

Section: Discussionmentioning

confidence: 99%

Chronic Oxidative Stress Increases Resistance to Doxorubicin-Induced Cytotoxicity in Renal Carcinoma Cells Potentially Through Epigenetic Mechanism

2015

View full text Add to dashboard Cite

Renal cell carcinoma is the most common form of kidney cancer and is highly resistant to chemotherapy. Although the role of oxidative stress in kidney cancer is known, the chemotherapeutic response of cancer cells adapted to chronic oxidative stress is not clear. Hence, the effect of oxidative stress on sensitivity to doxorubicin-induced cytotoxicity was evaluated using an in vitro model of human kidney cancer cells adapted to chronic oxidative stress. Results of MTT-and anchorage-independent growth assays and cell cycle analysis revealed significant decrease in sensitivity to doxorubicin in Caki-1 cells adapted to oxidative stress. Changes in the expression of genes involved in drug transport, cell survival, and DNA repair-dependent apoptosis further confirmed increased resistance to doxorubicin-induced cytotoxicity in these cells. Decreased expression of mismatch repair (MMR) gene MSH2 in cells exposed to oxidative stress suggests that loss of MMR-dependent apoptosis could be a potential mechanism for increased resistance to doxorubicin-induced cytotoxicity. Additionally, downregulation of HDAC1, an increase in the level of histone H3 acetylation, and hypermethylation of MSH2 promoter were also observed in Caki-1 cells adapted to chronic oxidative stress. DNA-demethylating agent 5-Aza-2dC significantly restored the expression of MSH2 and doxorubicin-induced cytotoxicity in Caki-1 cells adapted to chronic oxidative stress, suggesting the role of DNA hypermethylation in inactivation of MSH2 expression and consequently MMRdependent apoptosis in these cells. In summary, this study for the first time provides direct evidence for the role of oxidative stress in chemotherapeutic resistance in renal carcinoma cells potentially through epigenetic mechanism.

show abstract

“…Earlier, a study in DN was published that has utilized transcriptome profiling of fibroblasts from 100 type 1 diabetes patients from the longstanding Genetics of Kidneys in Diabetes cohort. It has suggested that patients who were protected from DN might undergo more robust epigenetic modifications resulting in enriched expression of genes involved in cell healing and repair pathways, and that epigenetic factors play a role in DN risk 77 .…”

Section: Studies Regarding Epigenetic Factors In Human Diabetic Nephrmentioning

confidence: 99%

Protective factors as biomarkers and targets for prevention and treatment of diabetic nephropathy: From current human evidence to future possibilities

Nowak

2020

J of Diabetes Invest

View full text Add to dashboard Cite

Although hyperglycemia, high blood pressure and aging increase the risk of developing kidney complications, some diabetes patients exposed to these risk factors do not develop kidney disease, suggesting the presence of endogenous protective factors. There is a growing need to understand these factors determining protection of the kidney in order to improve the design of preventive strategies and to enhance the processes responsible for renoprotection. The aim of this review was to present the existing molecular and epidemiological data on factors showing protective effects in diabetic kidney disease, and to summarize the evidence regarding their potential in the area of future clinical diagnostics, therapeutics and early preventive strategies. These include transcriptomic and proteomic studies regarding the anti‐inflammatory, anti‐fibrotic and regenerative factors that were associated with slower progression of renal function loss. Another focus is the new evidence regarding the evaluation of alterations in the regulatory epigenome and its involvement in the risk of diabetic kidney disease. Further effort is required to validate and extend these findings, and to define their potential for clinical implementation in the future.

show abstract

Differential Gene Expression in Diabetic Nephropathy in Individuals With Type 1 Diabetes

Abstract: Together, these data suggest that SF from T1D patients undergo epigenetic modifications resulting in increased expression of genes in healing and repair pathways. These responses, much more robust in patients protected from DN, suggest that epigenetic factors are important in DN risk.

Cited by 19 publications

References 35 publications

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

Chronic Oxidative Stress Increases Resistance to Doxorubicin-Induced Cytotoxicity in Renal Carcinoma Cells Potentially Through Epigenetic Mechanism

Protective factors as biomarkers and targets for prevention and treatment of diabetic nephropathy: From current human evidence to future possibilities

Contact Info

Product

Resources

About