Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy

Zhao, Liang; Zhao, Jun; Wang, Xueling; Chen, Zhuo; Peng, Kexin; Lu, Xiaohan; Meng, Linghang; Liu, Gang; Guan, Guangju; Wang, Fei

doi:10.1152/physiolgenomics.00082.2016

Cited by 34 publications

(25 citation statements)

References 30 publications

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“…Decreased GEnCs causes glomerular filtration dysfunction and proteinuria [26]. More important, EndMT plays a vital role in endothelial dysfunction, which [2,27]. In our study, we found that melatonin suppressed EndMT of GEnCs in diabetic nephropathy.…”

Section: Discussionsupporting

confidence: 51%

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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Section: Discussionsupporting

confidence: 51%

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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“…He et al (35) demonstrated that SRF promotes EMT in human peritoneal mesothelial cells. SRF also provokes EMT in renal tubular epithelial cells of diabetic nephropathy (36), and it induces EMT in hepatocellular carcinoma, prostate cancer, and gastric cancer (37). Therefore, SRF has a significant role in EMT and cancer metastasis.…”

Section: Discussionmentioning

confidence: 99%

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

2018

Int J Mol Med

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“…It has been shown that SRF is closely correlated to renal fibrosis in diabetic nephropathy and plays an important role in EMT in many types of renal cells, such as podocytes, 23 TECs 3 and glomerular endothelial cells. 24 Remarkably, SRF level and activation were increased in RCC cells (Fig. 2).…”

Section: Discussionmentioning

confidence: 81%

Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial–mesenchymal transition

Zhao¹,

Li²,

Jiang³

et al. 2020

Int J of Urology

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Objective To explore the regulation and function of serum response factor in epithelial–mesenchymal transition in renal cell carcinoma. Methods First, bioinformatics analysis of human renal cell carcinoma tissues was carried out. Then, the expression of serum response factor, mesenchymal markers (N‐cadherin, vimentin and fibronectin) and epithelial markers (zonula occludens‐1 and epithelial cadherin) was examined in 786‐O cells (a human renal cell carcinoma cell line). Serum response factor was overexpressed with pcDNA‐serum response factor plasmid, and suppressed by CCG‐1423 (a small molecule inhibitor of serum response factor) to study how serum response factor affects epithelial–mesenchymal transition in renal cell carcinoma. A xenograft nude mouse model was established to explore whether serum response factor affected the tumorigenic ability of renal cell carcinoma cells. Results Serum response factor interacted with several important differentially expressed genes in renal cell carcinoma. In 786‐O cells, serum response factor, N‐cadherin, vimentin and fibronectin were upregulated, whereas zonula occludens‐1 and epithelial cadherin were downregulated. Serum response factor upregulation in 786‐O cells increased the Snail expression. Serum response factor suppression reduced Snail induction, and migration and invasion in renal cell carcinoma, which decreased the xenograft tumor volume. Conclusions Serum response factor is a critical transcription factor in human renal cell carcinoma. Increased serum response factor activity induces epithelial–mesenchymal transition, migration and invasion in 786‐O cells, and facilitates the progression of renal cell carcinoma. Targeting serum response factor with CCG‐1423 might be an attractive therapeutic strategy for renal cell carcinoma.

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Serum response factor induces endothelial-mesenchymal transition in glomerular endothelial cells to aggravate proteinuria in diabetic nephropathy

Cited by 34 publications

References 30 publications

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

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

Suppressing serum response factor inhibits invasion in cervical cancer cell lines via regulating Egr‑1 and epithelial-mesenchymal transition

Serum response factor increases renal cell carcinoma migration and invasion through promoting epithelial–mesenchymal transition

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