Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus

Shan, Qun; Zheng, Gui‐Hong; Zhu, Aihua; Cao, Li; Lü, Jun; Wu, Dongmei; Zhang, ZiFeng; Fan, Shao‐Hua; Sun, Chunhui; Hu, Bin; Zheng, Yuxin

doi:10.1016/j.taap.2016.06.010

Cited by 43 publications

(33 citation statements)

References 42 publications

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“…A significant increase of hsa-miR-10a was observed with the knockdown of HDAC3 with siRNA, resulting in decrease of CREB1 the target of miR-10a, and fibronectin (FN) expression in kidney of HFD/STZ mice 113 . On the contrary, over expression of HDAC3 decreased miR-10a content, enhanced albumin-to-creatinine (ACR) value, CREB1 and FN in mice.…”

Section: Resultsmentioning

confidence: 99%

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T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders

Rani

Mittal

Pramanik

et al. 2017

Sci Rep

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We performed integrative analysis of genes associated with type 2 Diabetes Mellitus (T2DM) associated complications by automated text mining with manual curation and also gene expression analysis from Gene Expression Omnibus. They were analysed for pathogenic or protective role, trends, interaction with risk factors, Gene Ontology enrichment and tissue wise differential expression. The database T2DiACoD houses 650 genes, and 34 microRNAs associated with T2DM complications. Seven genes AGER, TNFRSF11B, CRK, PON1, ADIPOQ, CRP and NOS3 are associated with all 5 complications. Several genes are studied in multiple years in all complications with high proportion in cardiovascular (75.8%) and atherosclerosis (51.3%). T2DM Patients’ skeletal muscle tissues showed high fold change in differentially expressed genes. Among the differentially expressed genes, VEGFA is associated with several complications of T2DM. A few genes ACE2, ADCYAP1, HDAC4, NCF1, NFE2L2, OSM, SMAD1, TGFB1, BDNF, SYVN1, TXNIP, CD36, CYP2J2, NLRP3 with details of protective role are catalogued. Obesity is clearly a dominant risk factor interacting with the genes of T2DM complications followed by inflammation, diet and stress to variable extents. This information emerging from the integrative approach used in this work could benefit further therapeutic approaches. The T2DiACoD is available at www.http://t2diacod.igib.res.in/.

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Section: Resultsmentioning

confidence: 99%

“…On the contrary, over expression of HDAC3 decreased miR-10a content, enhanced albumin-to-creatinine (ACR) value, CREB1 and FN in mice. To sum up,it has been elucidated that HDAC3 /miR-10a/ CREB1 serves a new method underlying kidney injury,providing potential therapeutic target in type 2 diabetes 113 .…”

Section: Resultsmentioning

confidence: 99%

T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders

Rani

Mittal

Pramanik

et al. 2017

Sci Rep

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“…Xie et al reported that miR-128-3p improved the acute kidney injury via inhibiting cell apoptosis [18]. Previous study showed that miR-10awas played an important role in extracellular matrix accumulation in the kidney of diabetic mellitus in which the level of miR-10a decreased after high fat diet administration [20]. Another research reported that the level of urinary miR-10a was positively correlated with the degree of kidney injury induced by renal I/R.…”

Section: Discussionmentioning

confidence: 99%

Mir10a overexpression aggravates the renal ischemia-reperfusion injury associated with a decrease in PIK3CA

Zhang

et al. 2020

Preprint

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Abstract Background: To investigate the effect of miR-10a on the renal tissues with ischemia-reperfusion (I/R) injury in rats and explore the underlying mechanisms of miR-10a in the HK-2 cells of hypoxia-reoxygenation. Methods: The miR-10a level was measured in renal tissues with I/R rats by RT-PCR. In order to research the role of miR-10a in the renal tissues, miR-10 agonist and miR-10a antagonist were used to treat I/R rats. The levels of serum creatinine (Scr) and blood urea nitrogen (BUN) in serum, renal histopathology, apoptosis of cells in renal tissues were analyzed, separately. The phosphatidylinositol 3-kinase (PI3K)/Akt pathway related proteins were measured by Western blot. The HK-2 cell was cultured to study the mechanism of miR-10a in the model of hypoxia-reoxygenation. The dual luciferase reporter gene assay was used to confirm the PI3K p100 catalytic subunit α (PIK3CA) was a target gene of miR-10a. Results: After renal I/R injury in rats, the miR-10a expression was significantly increased (p<0.05). Injection of miR-10a agonist significantly aggravated the injury of renal and raised the apoptosis of cells in renal in rats with renal I/R injury (p<0.05). However, administration of miR-10a antagonist obviously improved the injury of renal, decreased the renal cells apoptosis and inhibited the PI3K/Akt pathway activity (p<0.05). In vitro experiments, the negative relation between PIK3CA and miR-10a was confirmed. Further, overexpression of miR-10a significantly decreased the proliferation of HK-2 cells, and increased the cells apoptosis via up-regulating PI3K/Akt pathway (p<0.05). Conclusion: miR-10a could aggravate the renal I/R injury associated with a decrease in PIK3CA/PI3K/Akt pathway.

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“…Growing evidences indicated that HDAC3 is related to diabetes and the complications, including diabetic liver lesions, diabetic aortic atherosclerosis [9], diabetic osteoporosis [10], diabetic cardiomyopathy, diabetic cerebral ischemia reperfusion model [11], and diabetic nephropathy model [12]. Meanwhile, HDAC3 activity has been associated with the apoptosis of RGCs in models of optic nerve damage [13].…”

Section: Introductionmentioning

confidence: 99%

“…Db/db mouse has been widely used as a T2DM model to investigate the pathogenesis of DR [14]. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner (8,12,16,18, and 25 weeks) by characterizing the process of retinal ganglion cell variation.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Expression of HDAC3 in db/db Mouse RGCs and Its Relationship with Apoptosis and Autophagy

Wang

Gao

et al. 2020

Journal of Diabetes Research

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Background. Diabetic retinopathy (DR) is a severe complication of diabetes mellitus. DR is considered as a neurovascular disease. Retinal ganglion cell (RGC) loss plays an important role in the vision function disorder of diabetic patients. Histone deacetylase3 (HDAC3) is closely related to injury repair and nerve regeneration. The correlation between HDAC3 and retinal ganglion cells in diabetic retinopathy is still unclear yet. Methods. To investigate the chronological sequence of the abnormalities of retinal ganglion cells in diabetic retinopathy, we choose 15 male db/db mice (aged 8 weeks, 12 weeks, 16 weeks, 18 weeks, and 25 weeks; each group had 3 mice) as diabetic groups and 3 male db/m mice (aged 8 weeks) as the control group. In this study, we examined the morphological and immunohistochemical changes of HDAC3, Caspase3, and LC3B in a sequential manner by characterizing the process of retinal ganglion cell variation. Results. Blood glucose levels and body weights of db/db mice were significantly higher than that of the control group, P < 0:01. Compared with the control group, the number of retinal ganglion cells decreased with the duration of disease increasing. HDAC3 expression gradually increased in RGCs of db/db mice. Caspase3 expression gradually accelerated in RGCs of db/db mice. LC3B expression dynamically changed in RGCs of db/db mice. HDAC3 was positively correlated with Caspase3 expression (r = 0:7424), P < 0:01. HDAC3 was positively correlated with LC3B expression (r = 0:7336), P < 0:01. Discussion. We clarified the dynamic expression changes of HDAC3, Caspase3, and LC3B in retinal ganglion cells of db/db mice. Our results suggest the HDAC3 expression has a positive correlation with apoptosis and autophagy.

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Epigenetic modification of miR-10a regulates renal damage by targeting CREB1 in type 2 diabetes mellitus

Cited by 43 publications

References 42 publications

T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders

T2DiACoD: A Gene Atlas of Type 2 Diabetes Mellitus Associated Complex Disorders

Mir10a overexpression aggravates the renal ischemia-reperfusion injury associated with a decrease in PIK3CA

Dynamic Expression of HDAC3 in db/db Mouse RGCs and Its Relationship with Apoptosis and Autophagy

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