miR-125a-5p Regulates Differential Activation of Macrophages and Inflammation

Banerjee, Sami; Cui, Huachun; Xie, Na; Tan, Zheng; Yang, Shanzhong; Icyuz, Mert; Thannickal, Victor J.; Abraham, Edward; Liu, Gang

doi:10.1074/jbc.m112.426866

Cited by 210 publications

(168 citation statements)

References 52 publications

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“…The overexpression of miR-125a-5p diminished the M1 phenotype expression induced by LPS but promoted the M2 marker expression induced by IL-4 [77]. In contrast, the knockdown of miR-125a-5p promoted M1 polarization, while diminished IL-4 induced M2 marker expression [80]. Moreover, miRNA let-7c is expressed at a higher level in M2 than in M1 macrophages [81].…”

Section: Muscle Regeneration: the Phase Of Necrosis And Inflammatorymentioning

confidence: 91%

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The Basis of Muscle Regeneration

Musarò

2014

Advances in Biology

103

125

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Muscle regeneration recapitulates many aspects of embryonic myogenesis and is an important homeostatic process of the adult skeletal muscle, which, after development, retains the capacity to regenerate in response to appropriate stimuli, activating the muscle compartment of stem cells, namely, satellite cells, as well as other precursor cells. Moreover, significant evidence suggests that while stem cells represent an important determinant for tissue regeneration, a "qualified" environment is necessary to guarantee and achieve functional results. It is therefore plausible that the loss of control over these cell fate decisions could lead to a pathological transdifferentiation, leading to pathologic defects in the regenerative process. This review provides an overview about the general aspects of muscle development and discusses the cellular and molecular aspects that characterize the five interrelated and time-dependent phases of muscle regeneration, namely, degeneration, inflammation, regeneration, remodeling, and maturation/functional repair.

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Section: Muscle Regeneration: the Phase Of Necrosis And Inflammatorymentioning

confidence: 91%

“…It has been reported that M2 macrophages express greater levels of miR-125a-5p than do M1 macrophages [80]. The overexpression of miR-125a-5p diminished the M1 phenotype expression induced by LPS but promoted the M2 marker expression induced by IL-4 [77].…”

Section: Muscle Regeneration: the Phase Of Necrosis And Inflammatorymentioning

confidence: 99%

The Basis of Muscle Regeneration

Musarò

2014

Advances in Biology

103

125

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“…2A). miR-125a was chosen for further investigation because several recent reports have highlighted its role(s) in macrophages (26)(27)(28)(29).…”

Section: Identification Of Mir-125a As a Downstream Molecule Of Notchmentioning

confidence: 99%

“…miR-125a is enriched in myeloid progenitors but at low level in monocytes (25,26), and is upregulated in M1 and downregulated in M2 macrophages (23,24). miR-125a is involved in differential activation of macrophages and other immune cells, as well as in myeloproliferative neoplasm (27)(28)(29)(30). In this study, we show that forced Notch activation in macrophages by conditional overexpressing Notch intracellular domain (NIC) was sufficient to support TAM differentiation but abrogate TAM functions, most likely through miR-125a, leading to repressed tumor growth in mice.…”

Section: Introductionmentioning

confidence: 99%

Forced Activation of Notch in Macrophages Represses Tumor Growth by Upregulating miR-125a and Disabling Tumor-Associated Macrophages

Zhao

Huang

et al. 2016

Cancer Research

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Tumor-associated macrophages (TAM) contribute greatly to hallmarks of cancer. Notch blockade was shown to arrest TAM differentiation, but the precise role and underlying mechanisms require elucidation. In this study, we employed a transgenic mouse model in which the Notch1 intracellular domain (NIC) is activated conditionally to define the effects of active Notch1 signaling in macrophages. NIC overexpression had no effect on TAM differentiation, but it abrogated TAM function, leading to repressed growth of transplanted tumors. Macrophage miRNA profiling identified a novel downstream mediator of Notch signaling, miR-125a, which was upregulated through an RBP-J-binding site at the first intronic enhancer of the host gene Spaca6A. miR-125a functioned downstream of Notch signaling to reciprocally influence polarization of M1 and M2 macrophages by regulating factor inhibiting hypoxia inducible factor-1a and IRF4, respectively. Notably, macrophages transfected with miR-125a mimetics increased phagocytic activity and repressed tumor growth by remodeling the immune microenvironment. We also identified a positive feedback loop for miR-125a expression mediated by RYBP and YY1. Taken together, our results showed that Notch signaling not only supported the differentiation of TAM but also antagonized their protumorigenic function through miR-125a. Targeting this miRNA may reprogram macrophages in the tumor microenvironment and restore their antitumor potential.

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“…Increasing miR-let-7c and miR-125a-5p level diminished the bactericidal activity of macrophages while enhancing the phagocytic activity to ingest apoptotic cells. In contrast, knockdown of miR-let-7c and miR-125a-5p in M-BMM decreased their ability to phagocytosis (89,90). Although, mainly focusing on cultured macrophages, these studies suggest that polarization of macrophages by gene therapy based on miR-223, miR-124, miR-125a-5p, and miR-let 7c may be a promising strategy for the treatment of inflammatory diseases.…”

Section: M1-to-m2 Repolarization As An Anti-inflammatory Therapeuticmentioning

confidence: 81%

Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

Talekar

Trần

Amiji

2015

AAPS J

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Abstract. With the advent of novel and personalized therapeutic approaches for cancer and inflammatory diseases, there is a growing demand for designing delivery systems that circumvent some of the limitation with the current therapeutic strategies. Nanoparticle-based delivery of drugs has provided means of overcoming some of these limitations by ensuring the drug payload is directed to the disease site and insuring reduced off-target activity. This review highlights the challenges posed by the solid tumor microenvironment and the systemic limitations for effective chemotherapy. It then assesses the basis of nanoparticle-based targeting to the tumor tissues, which helps to overcome some of the microenvironmental and systemic limitations to therapy. We have extensively focused on some of the tumor multidrug resistance mechanisms (e.g., hypoxia and aerobic glycolysis) that contribute to the development of multidrug resistance and how targeted nano-approaches can be adopted to overcome drug resistance. Finally, we assess the combinatorial approach and how this platform has been used to develop multifunctional delivery systems for cancer therapy. The review article also focuses on inflammatory diseases, the biological therapies available for its treatment, and the concept of macrophage repolarization for the treatment of inflammatory diseases.

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miR-125a-5p Regulates Differential Activation of Macrophages and Inflammation

Cited by 210 publications

References 52 publications

The Basis of Muscle Regeneration

The Basis of Muscle Regeneration

Forced Activation of Notch in Macrophages Represses Tumor Growth by Upregulating miR-125a and Disabling Tumor-Associated Macrophages

Translational Nano-Medicines: Targeted Therapeutic Delivery for Cancer and Inflammatory Diseases

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