MicroRNA-21 contributes to high glucose-induced fibrosis in peritoneal mesothelial cells in rat models by activation of the Ras-MAPK signaling pathway via Sprouty-1
Authors: Tian-Jun Guan
Lin Xu
Qian Yang
Qing Gao
Journal: Journal of Cellular Physiology (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: ERK; JNK; RAS-MAPK signaling pathway; Sprouty-1; apoptosis
Affiliations: Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China.

Abstract:  Peritoneal fibrosis remains to be one of the most severe causes of failure in continuous peritoneal dialysis. The current study cultured peritoneal mesothelial cells in high glucose to stimulate the environment of peritoneal fibrosis model in rats, and investigate whether microRNA-21 (miR-21) targeting Sprouty-1 affects high glucose-induced fibrosis in peritoneal mesothelial cells via the rennin angiotensin system (Ras)-mitogen-activated protein kinase (MAPK) signaling pathway, as well as potential mechanisms. Peritoneal tissues in fibrosis rats were collected to extract peritoneal mesothelial cells, which, after in vitro culture, were transfected with a series of mimic or inhibitor of miR-21, or the small interfering RNA (siRNA) against Sprouty-1. Reverse-transcription quantitative polymerase chain reaction and western blot analyses were performed to determine the levels of related genes or proteins. MTT assay and flow cytometry were conducted to observe the cell viability and cell apoptosis of peritoneal mesothelial cells. Dual-luciferase reporter gene assay revealed that Sprouty-1 is the target gene of miR-21. Peritoneal fibrosis manifested with elevated miR-21, extracellular-signal-regulated kinase (ERK), c-Jun NH2-terminal protein kinase (JNK), RAS and p38MAPK but reduced Sprouty-1. Cells transfected with miR-21 mimic exhibited decreased Sprouty-1 expressions, but increased levels of ERK, JNK, RAS, and p38MAPK. As for cellular process, miR-21 mimic or siRNA against Sprouty-1 exposure reduced cell viability, which resulted in more cells arrested at the G1 stage, and induced apoptosis. In contrast, miR-21 inhibitor exposure was observed to have induced effects on peritoneal mesothelial cells. These key findings provide evidence that miR-21 inhibits Sprouty-1 to promote the progression of fibrosis in peritoneal mesothelial cells by activating the Ras-MAPK signaling pathway. 

Retracted: Yes

PubPeer comments:
 Fig 5(b).  MiRu201021 decreased Sproutyu20101 levels but increased levels of ERK, JNK, RAS, and p38MAPK.... (b) gray value of Sproutyu20101 and related proteins of Rasu2013MAPK signaling pathway in each group . ![file] Blue rectangle marks a distinctive loading control that appears in a number of otherwise-unrelated papers. Here, Fig 7(b) from [Luo et al (2018)] . ![] Figs 9A from [Wu et al (2018a)] and 5C from [Wu et al (2018)] . Many other examples in the linked threads. ![] , 
 Fig 7(a).  Flow cytometry was used to detect the differences of cell cycle distribution and apoptosis caused by miRu201021 targeting Sproutyu20101. (a) The cell cycle distribution of each group after transfection . ![file] The plotting software has produced some unexpected overhangs in the cell-count histograms. , 
 Retracted [20 July 2021] . ---------------------------------------------- The above article, published online on 04 December 2018 in Wiley Online Library has been retracted by agreement between the journal s Editor in Chief, Prof. Dr. Gregg Fields, and Wiley Periodicals LLC. The retraction has been agreed following an investigation based on allegations raised by a third party. A detailed investigation revealed that several image elements of the experimental data were published elsewhere in a different scientific context. Thus, the editors consider the conclusions of this article to be invalid. ,