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

Kidney & Blood Pressure Research
Feng LiuJian Yin

Abstract

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. 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. 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 ...Continue Reading

Citations

Sep 11, 2019·Cardiovascular Research·Melanie S HulshoffGuido Krenning
May 18, 2020·Diabetes/metabolism Research and Reviews·Ehsan DehdashtianAzam Hosseinzadeh
May 26, 2020·BioFactors·Sasivimon Promsan, Anusorn Lungkaphin
Apr 14, 2020·Diabetology & Metabolic Syndrome·Mohammad Hossein PourhanifehSaeed Mehrzadi
May 28, 2020·Frontiers in Immunology·Rossana FranzinGiuseppe Castellano
Dec 23, 2020·Epigenomics·Mohammad Hossein PourhanifehAzam Hosseinzadeh
Dec 16, 2019·Drug Discovery Today·Prasanti Sharma, Kalyan Roy
Jan 19, 2021·BioMed Research International·Jinshi ZhangQiang He
Oct 31, 2020·Frontiers in Pharmacology·Marloes SolJan-Luuk Hillebrands
Dec 11, 2020·Evidence-based Complementary and Alternative Medicine : ECAM·Xiulan WangHongmei Chen
Dec 1, 2020·Visnyk Kyïvsʹkoho Nat︠s︡ionalʹnoho Universytetu Imeni Tarasa Shevchenka. Biolohii︠a︡·A StavniichukJohn D Imig
Jun 8, 2021·Frontiers in Cell and Developmental Biology·Roberta GiordoGianfranco Pintus
Oct 17, 2021·Diabetology & Metabolic Syndrome·Li ZhaoHualing Ruan

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