Molecular and Cellular Biochemistry

, Volume 454, Issue 1–2, pp 97–109 | Cite as

Genes interconnecting AMPK and TREM-1 and associated microRNAs in rotator cuff tendon injury

  • Finosh G. Thankam
  • Chandra S. Boosani
  • Matthew F. Dilisio
  • R. Michael Gross
  • Devendra K. AgrawalEmail author


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.


AMPK 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.

Supplementary material

11010_2018_3456_MOESM1_ESM.docx (70 kb)
Supplementary material 1 (DOCX 69 KB)


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Departments of Clinical & Translational Science and Orthopedic SurgeryCreighton University School of MedicineOmahaUSA
  2. 2.Department of Clinical & Translational ScienceThe Peekie Nash Carpenter Endowed Chair in MedicineOmahaUSA

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