Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Ma, Xingzhe; Liu, Ying; Wang, Qixue; Chen, Yuanli; Li, Mengyang; Li, Xiaoju; Xiang, Rong; Wei, Yuquan; Duan, Yajun; Han, Jihong

doi:10.1016/j.bbadis.2015.02.006

Cited by 19 publications

(13 citation statements)

References 46 publications

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“…Total RNA was extracted from cells followed by cDNA synthesis as described (22). Real-time PCR was conducted using SYBR Green PCR Master Mix (Bio-Rad) and the following primers: CH25H forward, 5′-ATGTTGACCACGTGGAAGGT-3′ and CH25H reverse, 5′-TGGGAACTGTTTTCTTTGGG-3′; GAPDH forward, 5′-ACAACTTTGGCATTGTGAA-3′ and GAPDH reverse, 5′-GATGCAGGGATGATGTTCTG-3′.…”

Section: Cdna Synthesis and Quantitative Real-time Pcrmentioning

confidence: 99%

Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol

Liu

Zhuo

Zhang

et al. 2018

Journal of Lipid Research

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25-Hydroxycholesterol (25HC) is produced in cells by an enzymatic reaction catalyzed by cholesterol 25-hydroxylase (CH25H). 25HC can function as an inhibitor of viral infection and an endogenous agonist of liver X receptor (LXR), a ligand-activated transcription factor. The previous studies have demonstrated the multiple biological functions of 25HC. For instance, CH25H expression and 25HC production are involved in immunological processes (1). Stimulation of macrophage Toll-like receptors can induce CH25H expression and consequently enhance 25HC production/ secretion and suppress immunoglobulin A production (2). CH25H expression in bone marrow-derived dendritic cells and macrophages can be upregulated by interferons (IFNs) (3). This finding results in the identification of CH25H as one of the IFN-stimulated genes and 25HC as a potent inhibitor of viral infection (4, 5). In vitro, 25HC can inhibit growth of multiple viruses in cells by blocking viral entry. The inhibition of viral infection by IFNs is also related to induction of CH25H expression and 25HC production (4, 5). In vivo, CH25H-deficient mice are more susceptible to viral infection than wild-type mice (4). 25HC also functions as an amplifier of inflammatory signaling via the activator protein 1 signaling pathway (6) and mediates the negative-feedback pathway of IFN signaling on interleukin 1 family cytokine production and inflammasome activity (7). Besides antiviral infection (4, 5, 8-11), 25HC can regulate lipid/cholesterol metabolism by interacting with sterol regulatory element-binding proteins or LXR (12). LXR plays various biological roles, particularly in lipid metabolism Abstract Production of 25-hydroxycholesterol (25HC), a potent inhibitor of viral infection, is catalyzed by cholesterol 25-hydroxylase (CH25H). We previously reported that 25HC induced CH25H expression in a liver X receptor (LXR)dependent manner, implying that LXR can play an important role in antiviral infection. In this study, we determined that activation of LXR by 25HC or synthetic ligands [T0901317 (T317) or GW3965] inhibited infection of herpes simplex virus type 1 (HSV-1) or MLV-(VSV)-GFP in HepG2 cells or RAW 264.7 macrophages. Genetic deletion of LXR, LXR, or CH25H expression in HepG2 cells by CRISPR/Cas9 method increased cell susceptibility to HSV-1 infection and attenuated the inhibition of LXR on viral infection. Lack of interferon (IFN)- expression also increased cell susceptibility to viral infection. However, it attenuated, but did not block, the inhibition of LXR on HSV-1 infection. In addition, expression of CH25H, but not IFN-, was inversely correlated to cell susceptibility to viral infection and the antiviral actions of LXR. Metabolism of 25HC into 25HC-3-sulfate (25HC3S) by cholesterol sulfotransferase-2B1b moderately reduced the antiviral actions of 25HC because 25HC3S is a weaker inhibitor of HSV-1 infection than 25HC. Furthermore, administration of T317 to BALB/c mice reduced HSV-1 growth in mouse tissues. Taken together, we demonstrate an antiviral s...

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Section: Cdna Synthesis and Quantitative Real-time Pcrmentioning

confidence: 99%

Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol

Liu

Zhuo

Zhang

et al. 2018

Journal of Lipid Research

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“…The potential side effects in men are infertility and gynecomastia (71). Ma et al reported that tamoxifen might cause hernia development in mice by activating matrix metalloproteinase expression (72). These interesting findings create an intersection for hernia and cancer and future studies could provide more surprising results on this topic.…”

Section: Discussionmentioning

confidence: 99%

Hernia and Cancer: The Points Where the Roads Intersect

Kulaçoğlu¹,

Köckerling

2019

Front. Surg.

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Introduction: This review aimed to present common points, intersections, and potential interactions or mutual effects for hernia and cancer. Besides direct relationships, indirect connections, and possible involvements were searched. Materials and Methods: A literature search of PubMed database was performed in July 2018 as well as a search of relevant journals and reference lists. The total number of screened articles was 1,422. Some articles were found in multiple different searches. A last PubMed search was performed during manuscript writing in December 2018 to update the knowledge. Eventually 427 articles with full text were evaluated, and 264 included, in this review. Results: There is no real evidence for a possible common etiology for abdominal wall hernias and any cancer type. The two different diseases had been found to have some common points in the studies on genes, integrins, and biomarkers, however, to date no meaningful relationship has been identified between these points. There is also some, albeit rather conflicting, evidence for inguinal hernia being a possible risk factor for testicular cancer. Neoadjuvant or adjuvant therapeutic modalities like chemotherapy and radiotherapy may cause postoperative herniation with their adverse effects on tissue repair. Certain specific substances like bevacizumab may cause more serious complications and interfere with hernia repair. There are only two articles in PubMed directly related to the topic of “hernia and cancer.” In one of these the authors claimed that there was no association between cancer development and hernia repair with mesh. The other article reported two cases of squamous-cell carcinoma developed secondary to longstanding mesh infections. Conclusion: As expected, the relationship between abdominal wall hernias and cancer is weak. Hernia repair with mesh does not cause cancer, there is only one case report on cancer development following a longstanding prosthetic material infections. However, there are some intersection points between these two disease groups which are worthy of research in the future.

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“…9). In some studies, the fibrotic modulation property of tamoxifen has been reported to act via the TGF-b [31][32][33][34] or ERK1/2 pathway [35,36]. However, the influence of tamoxifen on TGF-b signaling is still under debate, as opposing effects have been observed in different species and cell types [35,37].…”

Section: Discussionmentioning

confidence: 99%

Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination

Clappier

Kleiter

et al. 2019

FEBS Open Bio

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Tamoxifen is very successfully used for the induction of CreERT‐mediated genomic recombination in conditional mouse models. Recent studies, however, indicated that tamoxifen might also affect the fibrotic response in several disease models following administration, both in vitro and in vivo. In order to investigate a possible effect of tamoxifen on pancreatic fibrogenesis and to evaluate an optimal treatment scheme in an experimental pancreatitis mouse model, we administered tamoxifen by oral gavage to both male and female C57BL/6J mice and then waited for different periods of time before inducing chronic pancreatitis by cerulein. We observed a sex‐specific and time‐dependent effect of tamoxifen on the fibrotic response as measured by collagen deposition and the number of myofibroblasts and macrophages. The findings of in vitro studies, in which cerulein was administrated with or without 4‐hydroxytamoxifen to stimulate primary murine female and male pancreatic stellate cells, supported our in vivo observations. Real‐time PCR also indicated that this effect may be related to differences in ERα expression between female and male stellate cells. Our data demonstrate that tamoxifen administration has unignorable side effects, which affect the experimental outcome in a cerulein‐based model of chronic pancreatitis in mice. We suggest a 2‐week waiting period before cerulein administration to reduce side effects to a minimum for the described fibrosis model in female mice.

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Tamoxifen induces the development of hernia in mice by activating MMP-2 and MMP-13 expression

Cited by 19 publications

References 46 publications

Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol

Activation of liver X receptor plays a central role in antiviral actions of 25-hydroxycholesterol

Hernia and Cancer: The Points Where the Roads Intersect

Tamoxifen affects chronic pancreatitis‐related fibrogenesis in an experimental mouse model: an effect beyond Cre recombination

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