Cited by 119Phagocytosis and Immune RegulationMicroRNA in disease regulationCardiac Fibrosis and Remodeling

MicroRNA-126 overexpression rescues diabetes-induced impairment in efferocytosis of apoptotic cardiomyocytes

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Suresh Babu, Sahana, Thandavarayan, Rajarajan A., Joladarashi, Darukeshwara, Jeyabal, Prince, Krishnamurthy, Shashirekha, Bhimaraj, Arvind, Youker, Keith A., Krishnamurthy, Prasanna·2016·Scientific Reports

Abstract

Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far. In the present study we found that invitro efferocytosis of ACM was impaired in macrophages from db/db (diabetic) mice. Macrophages exposed to high glucose (HG) decreases microRNA-126 (miR-126) expression with a corresponding increase in ADAM9 expression. Dual-luciferase reporter assay confirms that ADAM9 3′UTR contains miR-126 target site. ADAM9 inhibition reduces HG-induced proteolytic cleavage of Mer tyrosine receptor kinase (MerTK, a proto-oncogene that plays a critical role in phagocytosis), resulting in shedding of soluble-Mer (sMER) and loss of MERTK function. Over-expression of miR-126 attenuates HG-induced impairment of efferocytosis. Furthermore, human diabetic hearts show lower miR-126 expression with a corresponding increase in ADAM9 expression vs. normal counterparts. These data suggests that diabetes impairs efferocytosis of ACM and that strategies to enhance efferocytosis might attenuate diabetes-induced impairment in inflammation resolution and cardiac repair after injury.

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  • miR-126 overexpression attenuates high glucose-induced impairment of efferocytosis.

    “Babu et al. showed the next microRNA able to affect efferocytosis, miR-126 overexpression, attenuates high glucose-induced impairment of efferocytosis [218].”

    From MicroRNAs as Regulators of Phagocytosis (2022) · cites this paper as [218]

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Authors
Suresh Babu, S., Thandavarayan, R. A., Joladarashi, D., Jeyabal, P., Krishnamurthy, S., Bhimaraj, A., Youker, K. A., & Krishnamurthy, P.
Affiliations
  • Houston Methodist (US)
  • University of Alabama at Birmingham (US)
Corresponding author
Krishnamurthy, Prasanna
Venue
Scientific Reports
Published
2016-11-09
Volume
6
Issue
1
Pages
36207-36207
ISSN
2045-2322 (ISSN-L)
OpenAlex
W2549443412
Cited by
119
References
49
Citations by year
2026: 12 · 2025: 23 · 2024: 19 · 2023: 8 · 2022: 18 · 2021: 17 · 2020: 5 · 2019: 8 · 2018: 4 · 2017: 5
FWCI
3.44
Type
journal article
Language
en
Open access
Locations
  • Scientific Reports (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • American Heart Association (25860041, 15POST25710392, 16POST30780010, GRNT25860041)
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (R01HL116729)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
Keywords
miR-126, efferocytosis, diabetes mellitus, macrophages, ADAM9, MERTK, high glucose, db/db mice, inflammation resolution, cardiac repair, myocardial injury
MeSH terms
RAW 264.7 Cells, THP-1 Cells, c-Mer Tyrosine Kinase, Proto-Oncogene Mas, Animals, Diabetes Mellitus, Experimental, Gene Expression Regulation, Glucose, Humans, Macrophages, Membrane Proteins, Phagocytosis, Apoptosis, 3' Untranslated Regions, Myocytes, Cardiac, MicroRNAs, Mice, ADAM Proteins

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