title: Rho kinase pathway is likely responsible for the profibrotic actions of aldosterone in renal epithelial cells via inducing epithelial-mesenchymal transition and extracellular matrix excretion.
abstract: It has been demonstrated that aldosterone (ALD) plays a direct profibrotic role in the kidney but the underlying mechanism remains unclear. We examined the role of Rho kinase signal pathway in epithelial-mesenchymal transition (EMT) process and extracellular matirx (ECM) synthesis induced by ALD in human renal proximal tubular epithelial (HK-2) cells in vitro. Rho kinase and collagen I, III protein expressions were detected by ELISA. E-cadherin, α-smooth muscle actin (SMA), collagen_I and collagen III mRNA expressions were detected by real time PCR. E-cadherin, and α-SMA protein expressions were measured by Western blot. Our results showed that ALD could significantly activate the Rho kinase in HK-2 cells, while in the presence of mineralocorticoid receptor (MR) antagonist eplerenone and Rho kinase inhibitor Y27632, the Rho kinase protein expression were almost completely prevented. Exposure of HK-2 cells to ALD for 48 h induced EMT as evidenced by loss of E-cadherin, and de novo expression of α-SMA. The EMT was completely blocked by eplerenone and Y27632. Meanwhile, ALD could significantly increase the mRNA and protein expressions of collagen I, III in HK-2 cells when compared with the control group, while eplerenone and Y27632 could almost reverse these effects. These observations suggest that ALD can activate Rho kinase pathway and Rho kinase pathway is likely responsible for the profibrotic actions of ALD in renal proximal tubular epithelial cells via inducing EMT and ECM excretion.
authors: Department of Nephrology, Hainan General Hospital, Haikou, Hainan 570311, China.
authors: Jiali
authors: J
authors: Wei
authors: Zhuori
authors: Z
authors: Li
authors: Chunyang
authors: C
authors: Ma
authors: Feng
authors: F
authors: Zhan
authors: Wei
authors: W
authors: Wu
authors: Hui
authors: H
authors: Han
authors: Yun
authors: Y
authors: Huang
authors: Wenning
authors: W
authors: Li
authors: Daojun
authors: D
authors: Chen
authors: Youming
authors: Y
authors: Peng
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000450:Aldosterone / Q000494:pharmacology*; D000577:Amides / Q000494:pharmacology; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D000077545:Eplerenone; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D018161:Receptors, Mineralocorticoid / Q000737:chemistry / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000577:Amides; D015820:Cadherins; D024042:Collagen Type I; D024061:Collagen Type III; D000451:Mineralocorticoid Receptor Antagonists; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; C108830:Y 27632; D013148:Spironolactone; D000450:Aldosterone; D000077545:Eplerenone; D054460:rho-Associated Kinases