Effect of miR-495 on lower extremity deep vein thrombosis through the TLR4 signaling pathway by regulation of IL1R1
Authors: Feng Guo
Yu Zhao
Qiu Zeng
Zhi-Peng Yang
Ke-Cheng Tang
Jing Wang
Journal: Bioscience reports (2018)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Cell cycle; Femoral vein; IL1R1; Lower extremity deep vein thrombosis; MicroRNA-495
Affiliations: Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China., Department of General Surgery, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, P.R. China., Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China., Department of Vascular Surgery, Universitätsmedizin Mannheim Theodor Kutzer Ufer, Mannheim 1-368167, Germany., Department of Vascular Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China .

Abstract:  Lower extremity deep vein thrombosis (LEDVT), a common peripheral vascular disease caused by a blood clot in a deep vein is usually accompanied by swelling of the lower limbs. MicroRNAs (miRs) have been reported to play roles in LEDVT. We aimed to investigate the effect of miR-495 on LEDVT via toll-like receptor 4 (TLR4) signaling pathway through interleukin 1 receptor type 1 (IL1R1). LEDVT mouse model was established, and the femoral vein (FV) tissues were collected to detect expressions of miR-495, IL1R1, and TLR4 signaling-related genes. The expressions of both CD31 and CD34 (markers for endothelial progenitor cells) in the FV endothelial cells as well as the proportion of CD31+/CD34+ cells in peripheral blood were measured in order to evaluate thrombosis. The effect of miR-495 on cell viability, cell cycle, and apoptosis was analyzed. IL1R1 was confirmed as the target gene of miR-495. Besides, inhibiting the miR-495 expression could increase IL1R1 expression along with activating the TLR4 signaling pathway. The total number of the leukocytes along with the ratio of weight to length of thrombus in the FV tissue showed an increase. The overexpression of miR-495 could promote FV endothelial cell viability. By injecting agomiR-495 and antagomiR-495 in vivo, the number of leukocytes in the FV tissues and the ratio of weight to length of thrombus were significantly decreased in the mice injected with the overexpressed miR-495, and the IL1R1/TLR4 signaling pathway was inhibited. Collectively, overexpressed miR-495 directly promotes proliferation while simultaneously inhibiting apoptosis of FV endothelial cells, alleviating FV thrombosis by inhibiting IL1R1 via suppression of TLR4 signaling pathway. 

Retracted: No

PubPeer comments:
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 Although overlapping has been found in case of the histology samples of the Group-1(control,untreated mice) Group-2(treated with Gum Acacia microspheres), both groups do not exhibit any significant signs of apoptosis as depicted from the previous experiments. The cells treated with gum acacia microspheres and mock treated cells (control) do not exhibit any considerable cytotoxic effects (as depicted by MTT, FACS assay and Western Blot) on triple negative breast cancer cells. However, unfortunately some part of the histology slide of group-1 and group-2 has overlapped. But this is clearly unintentional and we regret that. So we are attaching herewith another histology picture of our group-2 sample which will be sent for erratum. ![file] , 
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 I personally do not think that there is any intentional aberration of results conducted by the author.The overlap is highly coincidental as is the case in many histological specimens.The scrutiny of histological samples cannot be so straight forward.Overlapping of some part does not conclusively proof that the authors have resorted to dishonest means.Though I would like to appreciate the authors for their reply.However I do not think an erratum submission is required,although this totally depends on the authors.And lastly my learned peer, Hoya Camphorifolia must have overlooked that the authors are giving the histology from the same group of mice.Hence field overlap is quite natural. , 
 #4 I don t think anyone intends to accuse the authors of dishonesty! Instead, there has been a mix-up of slides, so that two overlapping enlargements of one slide have been mistakenly used to illustrate two separate conditions. Everyone will be grateful for the authors replacement of one of the slides with an image from the appropriate condition. However, in their proposed replacement, if two of the panels are again overlapping enlargements from a single larger image, this is not ideal as an illustration of the repeated appearance - that was what I intended to convey in comment #3. , 
 Author give corrigendum to their paper  Corrigendum to u201cFolic acid conjugated curcumin loaded biopolymeric gum acacia microsphere for triple negative breast cancer therapy in invitro and invivo modelu201d [Mater. Sci. Eng. C (2019) 204u2013216] which is good, but again author submit same blot i in two different name. In fig 6. **bcl2 and cleaved caspase 3 blot are same and just reverse to another**. This is quite disappointing that in even in erratum author gives the same blot in two different name. this need to change![file] . , 
 Author copy FACS data of Fig no 3C of the paper  Folic acid conjugated curcumin loaded biopolymeric gum acacia microsphere for triple negative breast cancer therapy in invitro and invivo model to **fig no. 4 a of  Anti-cancer potential of (1,2-dihydronaphtho[2,1-b]furan-2-yl)methanone derivatives . ![file] ![file] , 
 ![file] ![file] The indicated fields don t resemble each other. ,