Dataset Information

MALAT1: A regulator of inflammatory cytokines in diabetic complications.

ABSTRACT:

Objectives and design

In this study, we examined the role of MALAT1, a highly conserved nuclear long non-coding RNA molecule, in chronic diabetic complications affecting the heart and kidneys using both in vitro and in vivo models: human endothelial cell culture and a Malat1 knockout mice model.

Results

Findings from our in vitro experiments demonstrated that MALAT1 was predominantly localized to nuclear speckles in endothelial cells and MALAT1 expression was significantly increased following incubation with high glucose in association with increased expression of inflammatory cytokines. As for our in vivo experiments, we used Malat1 knockout mice and wild-type controls with or without streptozotocin-induced diabetes over 2 months of follow-up, where all of our diabetic animals showed hyperglycaemia and polyuria. Examination of cardiac and renal tissues demonstrated altered MALAT1 RNA expression in wild-type diabetic animals. Such changes were associated with augmented production of downstream inflammatory molecules at the mRNA and protein levels. Diabetes-induced elevations of inflammatory markers were significantly decreased in Malat1 knockout diabetic animals. In addition to transcript and protein analyses, we examined functional changes in the heart and kidneys. Organ functions were affected in the wild-type diabetic mice but were rescued in Malat1 knockout mice.

Conclusions

Taken together, findings from this study will provide direct evidence and insight into the importance of MALAT1 in the pathogenesis of chronic diabetic complications involving the heart and kidneys.

SUBMITTER: Gordon AD

PROVIDER: S-EPMC6354803 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Publications

MALAT1: A regulator of inflammatory cytokines in diabetic complications.

Gordon Andrew Devon AD Biswas Saumik S Feng Biao B Chakrabarti Subrata S

Endocrinology, diabetes & metabolism 20180118 2

<h4>Objectives and design</h4>In this study, we examined the role of MALAT1, a highly conserved nuclear long non-coding RNA molecule, in chronic diabetic complications affecting the heart and kidneys using both in vitro and in vivo models: human endothelial cell culture and a Malat1 knockout mice model.<h4>Results</h4>Findings from our in vitro experiments demonstrated that MALAT1 was predominantly localized to nuclear speckles in endothelial cells and MALAT1 expression was significantly increas ...[more]

PMID: 30815547

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Project description:ObjectiveAcute necrotic collection (ANC), acute peripancreatic fluid collection (APFC), pleural effusion, and ascites are common early complications of acute pancreatitis. This study aimed to investigate the relationship between 12 serum cytokines and the early complications and severity of acute pancreatitis (AP).MethodsWe retrospectively analyzed the clinical data of 307 patients with AP, and divided them into severe group and mild-to-moderate group according to the revised Atlanta classification. Propensity score matching was used to control for confounding factors. Binary logistic regression analysis was used to explore the relationship between cytokine levels and early complications of AP.ResultsSerum levels of interleukin (IL)-1β, IL-5, IL-6, IL-8, IL-10, IL-17, and tumor necrosis factor-α were significantly higher in the severe acute pancreatitis (SAP) group than in the non-SAP group (p < .05). After adjusting for confounding factors, the upper quartiles of IL-6, IL-8, and IL-10 were associated with an increased risk of ANC compared with those in the lowest quartile (IL-6: quartile 3, odds ratio [OR] = 3.99, 95% confidence interval [CI] = 1.95-8.16; IL-8: quartile 4, OR = 2.47, 95% CI = 1.27-4.84; IL-10: quartile 2, OR = 2.22, 95% CI = 1.09-4.56). APFC was associated with high serum levels of IL-6 (quartile 3, OR = 1.32, 95% CI = 1.02-1.72), pleural effusions were associated with high serum levels of IL-1β, IL-6, IL-8, and IL-10 (IL-1β: quartile 4, OR = 2.36, 95% CI = 1.21-4.58; IL-6: quartile 3, OR = 4.67, 95% CI = 2.27-9.61; IL-8: quartile 3, OR = 2.95, 95% CI = 1.51-5.79; IL-10: quartile 4, OR = 3.20, 95% CI = 1.61-6.36), and high serum levels of IL-6 and IL-10 were associated with an increased risk of ascites (IL-6: quartile 3, OR = 3.01, 95% CI = 1.42-6.37; IL-10: quartile 3, OR = 2.57, 95% CI = 1.23-5.37).ConclusionSerum cytokine levels, including IL-1β, IL-6, IL-8, and IL-10 may be associated with the occurrence of early complications of AP. In daily clinical practice, IL-6 may be the most worthwhile cytokine to be detected.

Dataset Information

MALAT1: A regulator of inflammatory cytokines in diabetic complications.

Objectives and design

Results

Conclusions

Publications

MALAT1: A regulator of inflammatory cytokines in diabetic complications.

Similar Datasets

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