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Genes interconnecting AMPK and TREM-1 and associated microRNAs in rotator cuff tendon injury
Finosh G Thankam1, Chandra S Boosani1, Matthew F Dilisio1
1Departments of Clinical & Translational Science and Orthopedic Surgery, Creighton University School of Medicine, Omaha, NE, 68178, USA.
Abstract:
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.
Insights
Fatty infiltration and inflammation in rotator cuff tendon injuries (RCTI) are linked to specific microRNAs (miRNAs). Understanding these miRNAs may lead to new therapeutic strategies for healing RCTI.
Area of Science:
- Biomedical Science
- Molecular Biology
- Orthopedics
Background:
- Rotator cuff tendon injuries (RCTI) involve fatty infiltration and inflammation, complicating healing.
- AMP-activated protein kinase (AMPK) and TREM-1 are upregulated in RCTI, but their epigenetic regulation by microRNAs (miRNAs) is unclear.
- Understanding miRNA roles in RCTI pathophysiology could offer therapeutic avenues.
Purpose of the Study:
- To investigate microRNAs (miRNAs) associated with fatty infiltration and inflammation in rotator cuff tendon injuries (RCTI).
- To identify potential miRNA targets within the AMPK and TREM-1 signaling pathways in RCTI.
Main Methods:
- Compared miRNAs in RCTI patients with (FI group) versus without (No-FI group) fatty infiltration and inflammation.
- Utilized NetworkAnalyst to analyze gene networks involving AMPK (PRKAA1), TREM-1, HIF1α, HMGB1, and AGER.
- Screened for miRNAs with fold change < -7.5 and ≥10 target genes.
Main Results:
- Identified 13 key miRNAs and 216 target genes potentially involved in RCTI-related fatty infiltration and inflammation.
- Established a network analysis connecting AMPK and TREM-1 pathways through specific miRNAs.
Conclusions:
- Specific miRNAs are implicated in the fatty infiltration and inflammation observed in RCTI.
- Further research into the biological activity of these identified miRNAs could facilitate the development of novel miRNA-based therapeutics for RCTI management.
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