Genes interconnecting AMPK and TREM-1 and associated microRNAs in rotator cuff tendon injury
- 6 Downloads
Fatty infiltration and inflammation delay the healing responses and raise major concerns in the therapeutic management of rotator cuff tendon injuries (RCTI). Our evaluations showed the upregulation of ‘metabolic check point’ AMPK and inflammatory molecule, TREM-1 from shoulder biceps tendons collected from RCTI subjects. However, the epigenetic regulation of these biomolecules by miRNAs is largely unknown and it is likely that a deeper understanding of the mechanism of action can have therapeutic potential for RCTI. Based on this background, we have evaluated the miRNAs from RCTI patients with fatty infiltration and inflammation (FI group) and compared with RCTI patients without fatty infiltration and inflammation (No-FI group). NetworkAnalyst was employed to evaluate the genes interconnecting AMPK and TREM-1 pathway, using PRKAA1 (AMPK), TREM-1, HIF1α, HMGB1, and AGER as input genes. The most relevant miRNAs were screened by considering the fold change below − 7.5 and the number of target genes 10 and more which showed 13 miRNAs and 216 target genes. The exact role of these miRNAs in the fatty infiltration and inflammation associated with RCTI is still unknown and the understanding of biological activity of these miRNAs can pave ways to develop miRNA-based therapeutics in the management of RCTI.
KeywordsAMPK signaling Fatty infiltration HMGB1 Inflammation miRNA Rotator cuff tendon injury TREM-1
This work was supported by the State of Nebraska LB506 Grant to DKA and Creighton University LB692 Grant to MFD. The research work of DK Agrawal is also supported by R01HL116042, R01HL120659 and R01HL144125 awards from the National Heart, Lung and Blood Institute, National Institutes of Health, USA. The content of this original research article is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the State of Nebraska.
Compliance with ethical standards
Conflict of interest
The authors have no conflict of interest to disclose.
- 28.Torres A, Torres K, Pesci A et al (2012) Deregulation of miR-100, miR-99a and miR-199b in tissues and plasma coexists with increased expression of mTOR kinase in endometrioid endometrial carcinoma. BMC Cancer 12:. https://doi.org/10.1186/1471-2407-12-369
- 31.Palagani A, Op de Beeck K, Naulaerts S et al (2014) Ectopic microRNA-150-5p transcription sensitizes glucocorticoid therapy response in MM1S multiple myeloma cells but fails to overcome hormone therapy resistance in MM1R cells. PLoS ONE 9:e113842. https://doi.org/10.1371/journal.pone.0113842 CrossRefPubMedPubMedCentralGoogle Scholar
- 34.Brogaard L, Heegaard PMH, Larsen LE et al (2016) Late regulation of immune genes and microRNAs in circulating leukocytes in a pig model of influenza A (H1N2) infection. Sci Rep 6:. https://doi.org/10.1038/srep21812
- 37.Bork-Jensen J, Thuesen A, Bang-Bertelsen C et al (2014) Genetic versus non-genetic regulation of miR-103, miR-143 and miR-483-3p expression in adipose tissue and their metabolic implications—a twin study. Genes 5:508–517. https://doi.org/10.3390/genes5030508 CrossRefPubMedPubMedCentralGoogle Scholar
- 39.Wu J, Ji A, Wang X et al (2015) MicroRNA-195-5p, a new regulator of Fra-1, suppresses the migration and invasion of prostate cancer cells. J Transl Med 13:. https://doi.org/10.1186/s12967-015-0650-6
- 47.Gheinani AH, Kiss B, Moltzahn F et al (2017) Characterization of miRNA-regulated networks, hubs of signaling, and biomarkers in obstruction-induced bladder dysfunction. JCI Insight 2:. https://doi.org/10.1172/jci.insight.89560
- 48.Ye E-A, Liu L, Jiang Y et al (2016) miR-15a/16 reduces retinal leukostasis through decreased pro-inflammatory signaling. J Neuroinflammation 13:. https://doi.org/10.1186/s12974-016-0771-8
- 57.Aranda JF, Madrigal-Matute J, Rotllan N, Fernández-Hernando C (2013) MicroRNA modulation of lipid metabolism and oxidative stress in cardiometabolic diseases. Free Radic Biol Med 64:31–39. https://doi.org/10.1016/j.freeradbiomed.2013.07.014 CrossRefPubMedPubMedCentralGoogle Scholar
- 58.Liu Z, Wang Y, Borlak J, Tong W (2016) Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades. Sci Rep 6:. https://doi.org/10.1038/srep23709
- 63.Blotta MH, Marshall JD, DeKruyff RH, Umetsu DT (1996) Cross-linking of the CD40 ligand on human CD4+ T lymphocytes generates a costimulatory signal that up-regulates IL-4 synthesis. J Immunol Baltim Md 1950 156:3133–3140Google Scholar