Hyperosmotic stress activates the expression of members of the miR-15/107 family and induces downregulation of anti-apoptotic genes in rat liver

Santosa, David; Castoldi, Mirco; Paluschinski, Martha; Sommerfeld, Annika; Häussinger, Dieter

doi:10.1038/srep12292

Cited by 18 publications

(18 citation statements)

References 60 publications

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“…Bacteria can enact changes in miR expression in cells (Jin et al, 2014, Naeem et al, 2012). Additionally, it has been shown that reactive oxygen species (ROS), for example triggered by bacteria in the ulcers, can induce the miR-15 family (Dhall et al, 2014, Dunnill et al, 2015, Santosa et al, 2015). Therefore, S. aureus -mediated induction of miR-15b-5p found in DFUs and infected acute wounds suggests this mechanism of action to inhibit healing.…”

Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers

Ramirez

Pastar

Jozic

et al. 2018

Journal of Investigative Dermatology

107

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Diabetic foot ulcers (DFUs) are a debilitating complication of diabetes in which bacterial presence, including the frequent colonizer Staphylococcus aureus, contributes to inhibition of healing. MicroRNAs (miRs) play a role in healing and host response to bacterial pathogens. However, the mechanisms by which miR response to cutaneous S. aureus contributes to DFU pathophysiology are unknown. Here, we show that S. aureus inhibits wound closure and induces miR-15b-5p in acute human and porcine wound models and in chronic DFUs. Transcriptome analyses of DFU tissue showed induction of miR-15b-5p to be critical, regulating many cellular processes, including DNA repair and inflammatory response, by suppressing downstream targets IKBKB, WEE1, FGF2, RAD50, MSH2, and KIT. Using a human wound model, we confirmed that S. aureus-triggered miR-15b-5p induction results in suppression of the inflammatory- and DNA repair-related genes IKBKB and WEE1. Inhibition of DNA repair and accumulation of DNA breaks was functionally confirmed by the presence of the pH2AX within colonized DFUs. We conclude that S. aureus induces miR-15b-5p, subsequently repressing DNA repair and inflammatory response, showing a mechanism of inhibition of healing in DFUs previously unreported, to our knowledge. This underscores a previously unknown role of DNA damage repair in the pathophysiology of DFUs colonized with S. aureus.

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Section: Discussionmentioning

confidence: 99%

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers

Ramirez

Pastar

Jozic

et al. 2018

Journal of Investigative Dermatology

107

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“…Dynamic expression of highly conserved miR‐15 members is associated with cellular pro‐apoptotic activity (Cimmino et al, ). It was also shown in rodents that when miR‐15 family are inhibited, they were protected against cardiomyocyte apoptosis after myocardial infarction (Hullinger et al, ), and miR‐15a was also linked to the control of responses of cells to stress (Santosa, Castoldi, Paluschinski, Sommerfeld, & Haussinger, ). The molecular mechanisms of how miR‐15a modulates sperm function in the bovine are yet unknown.…”

Section: Discussionmentioning

confidence: 99%

Sperm miR‐15a and miR‐29b are associated with bull fertility

et al. 2019

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MicroRNAs modulate male fertility by regulating gene expression. In this study, dynamics of sperm miR-15a, miR-29b and miR-34a from high fertility (HF) and low fertility (LF) bulls using RT-qPCR were evaluated. Bioinformatic tools were employed to ascertain genes of interest of the sperm miRNAs. The expression levels of p53, BCL2, BAX and DNMT1 in bull spermatozoa were determined by immunoblotting.MicroRNA levels of miR-15a and miR-29 were higher in LF sires when compared with those present in HF bulls. Expression levels of miR-34a did not differ between the two groups. We found an inverse correlation between miR-15a and bull fertility.MiR29-b was also negatively associated with fertility scores. BCL2 and DNMT1 were higher in HF bulls while BAX was higher in the LF group. Our data showed a positive correlation between BCL2 and bull fertility. In addition, DNMT1 was positively associated with bull fertility. Furthermore, levels of BAX were negatively linked with bull fertility scores. Identification of miRNAs found in the spermatozoa of sires with different in vivo fertility helps understand the alterations in the fertilising capacity from cattle and other mammals. These potential biomarkers can be used in reproductive biotechnology as fertility markers to assess semen quality and predict male fertility. K E Y W O R D S male fertility, microRNA, real-time quantitative RT-PCR, sperm How to cite this article: Menezes ESB, Badial PR, El Debaky H, et al. Sperm miR-15a and miR-29b are associated with bull fertility. Andrologia. 2020;52:e13412. https ://doi.

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“…The expression levels of miR-15a, miR-15b and miR-16 were increased in rat livers which perfused with hyperosmotic solution. Upregulated miR-15a, miR-15b and miR-16 contribute to cell death through the inhibition of anti-apoptotic genes, such as Bcl2, CD-1, protein carboxyl- O -methyltransferase (Pcmt1) [ 33 ]. miR-15 family regulates TGF-β signaling pathway by targeting TGFβr1, Smad3, Smad7, p38 and endoglin directly or indirectly in cardiac fibrosis [ 30 ].…”

Section: The Mir-15 Family Members Have a Positive Impact On Tgf-β Simentioning

confidence: 99%

The roles of microRNA families in hepatic fibrosis

Jiang

Wan

et al. 2017

Cell Biosci

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When hepatocytes are damaged severely, a variety of signaling pathways will be triggered by inflammatory factors and cytokines involving in the process of hepatic fibrosis. The microRNA (miRNA) family consists of several miRNAs which have the potential for synergistic regulation of these signaling pathways. However, it is poor to understand the roles of miRNA family as a whole in hepatic fibrosis. Increasing studies have suggested several miRNA families are related with activation of hepatic stellate cells and hepatic fibrosis through cooperatively regulating certain signaling pathways. During the process of hepatic fibrosis, miR-29 family primarily induces cell apoptosis by modulating phosphatidylinositol 3-kinase/AKT signaling pathway and regulates extracellular matrix accumulation. miR-34 family promotes the progression of hepatic fibrosis by inducing activation of hepatic stellate cells, while miR-378 family suppresses the process in Glis dependent manner. miR-15 family mainly promotes cell proliferation and induces apoptosis. The miR-199 family and miR-200 family are responsible for extracellular matrix deposition and the release of pro-fibrotic cytokines. These miRNA family members play pro-fibrotic or anti-fibrotic roles by targeting genes collectively or respectively which involve in hepatic fibrosis related signaling pathways and hepatic stellate cell activation. Thus, good understandings of molecular mechanisms which are based on miRNA families may provide new ideas for the molecular targeted therapy of hepatic fibrosis in the future.

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Hyperosmotic stress activates the expression of members of the miR-15/107 family and induces downregulation of anti-apoptotic genes in rat liver

Cited by 18 publications

References 60 publications

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers

Staphylococcus aureus Triggers Induction of miR-15B-5P to Diminish DNA Repair and Deregulate Inflammatory Response in Diabetic Foot Ulcers

Sperm miR‐15a and miR‐29b are associated with bull fertility

The roles of microRNA families in hepatic fibrosis

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