NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy

Shang, Jin; Zhang, Ya; Jiang, Yumin; Li, Zhenzhen; Duan, Yiqi; Wang, Luyao; Xiao, Jing; Zhao, Zhanzheng

doi:10.1016/j.bbrc.2017.01.155

Cited by 54 publications

(36 citation statements)

References 24 publications

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“…Trim11 also promotes cell proliferation and inhibits cell apoptosis in colon cancer (43). Although there have been no reports on Trim11 and DN, one study reported that Trim11 can enhance cell proliferation by activating the Mek/Erk signaling pathway (23), which is an established pathway in DN (44,45). Furthermore, our results show that H2k2 increased the expression of Trim11, promoted the phosphorylation of Mek and Erk, and then activated the Mek/ Erk signaling pathway.…”

Section: Discussionsupporting

confidence: 51%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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Evidence has shown that long noncoding RNAs (IncRNAs) in the competing endogenous RNA (ceRNA) network are involved in various diseases. However, there is a lack of studies of the ceRNA network in diabetic nephropathy (DN). In this study, we investigated the effect of IncRNAs on mesangial cell (MC) proliferation in DN‐related ceRNA networks. Differences in IncRNA and mRNA expression between DN and normal mouse kidney tissues were detected with RNA‐seq, and DN‐related IncRNA/mRNA/microRNA (miRNA) ceRNA networks were constructed by R3.4.3. Computational analysis was performed, and expression and interactions between the topological RNAs were detected by bioinformatics methods, real‐time quantitative PCR (qPCR), and luciferase assay. Cell proliferation ability was measured by 5‐ethynyl‐2′‐deoxyuridine (EdU) in MCs cultured under high‐ or low‐glucose conditions. Moreover, the effect of the topological key IncRNA histocompatibility 2 K region locus 2 (H2k2) H2k2 on MC proliferation via the miRNA (miR)‐449a/b/triplet motif 11 (Trim11)/Mek signaling pathway was examined by EdU, flow cytometry analysis, and Western blot. In total, 153 IncRNAs, 428 mRNAs, and 2242 interactions were included in the constructed DN‐related ceRNA network. There were 15 RNAs in the top 5% of degree and betweenness. The expression of IncRNA H2k2 and mRNA Trim11 in MCs was increased in DN, which is consistent with the results of RNA‐seq and real‐time qPCR in vivo and in vitro. miR‐449a and miR‐449b, which were down‐regulated in MCs cultured with high glucose, were selected for further analysis. The results of real‐time qPCR and luciferase assay revealed the IncRNA H2k2‐miR‐449a/b‐Trim11 interaction in MCs. In addition, the data showed that H2k2 regulates MC proliferation via the miR‐449ab/Trim11/Mek signaling pathway. Taken together, these results provide new insight into the association between the topological key IncRNA H2k2 in the DN‐related ceRNA network and the miR‐449a/b/Trim11/Mek signaling pathway during MC proliferation in DN.—Chen, W., Peng, R., Sun, Y., Liu, H., Zhang, L., Peng, H., Zhang, Z. The topological key IncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathy via the miR‐449a/b/Trim11/Mek signaling pathway. FASEB J. 33, 11492–11506 (2019). http://www.fasebj.org

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Section: Discussionsupporting

confidence: 51%

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

et al. 2019

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“…In the current study, we found that melatonin significantly inhibited EndMT in GEnCs exposed to TGF-β2. In previous literates the staining for endothelial markers in diabetic glomeruli seems to be discrepancy [17,32,33]. Our results showed that CD31 staining was reduced in glomeruli of diabetic rats.…”

Section: Discussionsupporting

confidence: 68%

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy

Liu

Zhang

et al. 2018

Kidney Blood Press Res

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Background/Aims: Endothelial-to-mesenchymal transition (EndMT) of glomerular endothelial cells (GEnCs) can induce albuminuria in diabetic nephropathy. Melatonin attenuates diabetic nephropathy, but its role and mechanism in EndMT of GEnCs in diabetic nephropathy remain unknown. Methods: The effect of melatonin on EndMT induced by transforming growth factor (TGF)-β2 in human renal GEnCs was determined by assaying the expression of endothelial marker cells (VE-cadherin and CD31) and mesenchymal cells (α-SMA and Snail), as well as monolayer permeability. The molecular mechanism of melatonin in these processes was focused on miR-497/ROCK signaling. Furthermore, the effect and mechanism of melatonin in EndMT were confirmed in glomeruli of rats with streptozotocin-induced diabetes. Results: Melatonin increased expression of VE-cadherin and CD31 and inhibited α-SMA and Snail levels that were altered by TGF-β2 in GEnCs. Melatonin treatment reduced expression and activity of ROCK1 and ROCK2, which suppressed TGF-β2-induced hyperpermeability of GEnCs and EndMT of GEnCs. Melatonin reduced ROCK1 and ROCK2 expression and activity in TGF-β2-stimulated GEnCs by enhancing expression of miR-497, which targets ROCK1 and ROCK2. Furthermore, we found that melatonin inhibited EndMT in glomeruli and albuminuria in rats with streptozotocin-induced diabetes. MiR-497 expression increased, whereas ROCK1 and ROCK2 expression and activity decreased in melatonin-treated diabetic rats. Conclusion: Melatonin attenuated EndMT of GEnCs via regulating miR-497/ROCK signaling in diabetic nephropathy. This study improves understanding of EndMT and the role of melatonin in diabetic nephropathy.

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“…15 Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was performed and protein was transferred to polyvinylidene fluoride membranes (Roche, Mannheim, Germany). Total protein was measured by the BCA protein assay kit (CWBiotech Co., Beijing, China).…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

“…Western blot was performed as previously described. 15 Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) was performed and protein was transferred to polyvinylidene fluoride membranes (Roche, Mannheim, Germany). Membranes were blocked in 3% non-fat milk for at least 2 hours at room temperature.…”

Section: Protein Extraction and Western Blot Analysismentioning

confidence: 99%

Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

Shang

Wang

Zhang

et al. 2019

J Cellular Molecular Medi

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Diabetic nephropathy (DN) is characterized by inflammation of renal tissue. Glomerular endothelial cells (GEnCs) play an important role in inflammation and protein leakage in urine in DN patients. Chemerin and its receptor ChemR23 are inducers of inflammation. The aim of this study was to investigate the function of chemerin/ChemR23 in GEnCs of DN patients. Immunohistochemical staining and qRT‐PCR were used to measure the expression of chemerin, ChemR23 and inflammatory factors in renal tissues of DN patients. Db/db mice were used as animal model. ChemR23 of DN mice was knocked down by injecting LV3‐shRNA into tail vein. Inflammation, physiological and pathological changes in each group was measured. GEnCs were cultured as an in vitro model to study potential signalling pathways. Results showed that expression of chemerin, ChemR23 and inflammatory factors increased in DN patients and mice. LV3‐shRNA alleviated renal damage and inflammation in DN mice. GEnCs stimulated by glucose showed increased chemerin, ChemR23 and inflammatory factors and decreased endothelial marker CD31. Both LV3‐shRNA and SB203580 (p38 MAPK inhibitor) attenuated chemerin‐induced inflammation and injury in GEnCs. Taken together, chemerin/ChemR23 axis played an important role in endothelial injury and inflammation in DN via the p38 MAPK signalling pathway. Suppression of ChemR23 alleviated DN damage.

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NOD2 promotes endothelial-to-mesenchymal transition of glomerular endothelial cells via MEK/ERK signaling pathway in diabetic nephropathy

Cited by 54 publications

References 24 publications

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

The topological key lncRNA H2k2 from the ceRNA network promotes mesangial cell proliferation in diabetic nephropathyviathe miR‐449a/b/Trim11/Mek signaling pathway

Melatonin Attenuates Endothelial-to-Mesenchymal Transition of Glomerular Endothelial Cells via Regulating miR-497/ROCK in Diabetic Nephropathy

Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy

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