miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6

Kasimu, Aziguli; Apizi, Xierenguli; Talifujiang, Dilibaier; Ma, Xin; Fang, Liping; Zhou, Xiangling

doi:10.1016/j.endien.2022.01.006

Cited by 5 publications

(7 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…After a 1-week habituation, the db/db mice were randomly assigned to four groups (n = 5): db/db, db/db + NC, db/db + miR-503-5p agomiR, and db/db + miR-503-5p antigomiR. For the administration of miRNA, we administered 5 nmol of miR-503-5p agomiR, 5 nmol of antigomiR, or 5 nmol of miR-NC (miRNA negative control) into the tail vein of db/db mice after anesthesia, as described previously 5 . The injection was administered every four days for a total of four injections.…”

Section: Methodsmentioning

confidence: 99%

“…Tactile and heat responsiveness were determined as previously described 5 . For mechanical allodynia assessment, the mechanical withdrawal threshold (MWT) of the sole of the foot of the mice in a chamber with a wire mesh floor was registered using an automatic dynamic plantar aesthesiometer (Ugo Basile, Varese, Italy).…”

Section: Methodsmentioning

confidence: 99%

“…Astrocyte activation is associated with neuropathic pain 4 . Inhibition of astrocyte activation can alleviate pain caused by diabetic peripheral neuropathy 5 , 6 . Therefore, regulating astrocyte activation may improve neuropathic pain.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

Guo,

Zeng,

Zhuang

et al. 2024

Sci Rep

View full text Add to dashboard Cite

Diabetic peripheral neuropathy (DPN) is a common complication of type 2 diabetes mellitus (T2DM) that causes peripheral and autonomic nervous system dysfunction. Dysregulation of miRNAs plays a crucial role in DPN development. However, the role of miR-503-5p in DPN remains unknown. Herein, T2DM mice (db/db) were used as a DPN model in vivo, and astrocytes isolated from db/db mice were induced with high glucose levels as a DPN model in vitro. MiR-503-5p expression was analyzed using qRT-PCR. GFAP, MCP-1, and SEPT9 protein levels were analyzed using western blotting and immunofluorescence. Luciferase assays were performed to investigate the interaction between miR-503-5p and SEPT9. We found that miR-503-5p expression decreased in the spinal cord of DPN model mice and astrocytes treated with high glucose (HG). The db/db mice displayed higher body weight and blood glucose, lower mechanical withdrawal threshold and thermal withdrawal latency, and higher GFAP and MCP-1 protein levels than db/m mice. However, tail vein injection of agomiR-503-5p remarkably reversed these parameters, whereas antigomiR-503-5p enhanced them. HG markedly facilitated GFAP and MCP-1 protein expression in astrocytes, whereas miR-503-5p mimic or inhibitor transfection markedly blocked or elevated GFAP and MCP-1 protein expression, respectively, in astrocytes with HG. SEPT9 was a target of miR-503-5p. In addition, SEPT9 protein levels were found to be elevated in db/db mice and astrocytes treated with HG. Treatment with agomiR-503-5p and miR-503-5p mimic was able to reduce SEPT9 protein levels, whereas treatment with antigomiR-503-5p and miR-503-5p inhibitor led to inhibition of the protein. Furthermore, SEPT9 overexpression suppressed the depressing effect of miR-503-5p overexpression in astrocytes subjected to HG doses. In conclusion, miR-503-5p was found to alleviate peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 expression.

show abstract

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

Guo,

Zeng,

Zhuang

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…It was found that a number of miRNAs secreted as part of EVs are involved in the pathogenesis of diabetic retinopathy and neuropathy, and in the future, they can also be useful as early and reliable markers of these complications [ 11 , 12 , 13 ].…”

Section: Proteins and Mirnas Of Extracellular Vesicles (Evs) As Bioma...mentioning

confidence: 99%

The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy

Yunusova

Popova

Udintseva

et al. 2023

CIMB

View full text Add to dashboard Cite

Extracellular vesicles (EVs) as membrane structures of cellular origin participating in intercellular communication are involved in the molecular mechanisms of the development of various variants of polyneuropathy. Taking into account the increasing role of the protein corona of EVs and protein-protein interactions on the surface of EVs in the pathogenesis of various diseases, we focused our attention in this review on the role of intravesicular proteins and the protein corona of EVs in the development of chemotherapy-induced polyneuropathy (CIPN). It has been shown that EVs are effectively internalized by the mechanisms of endocytosis and macropinocytosis by neurocytes and glial cells, carry markers of insulin resistance, functionally active proteins (receptors, cytokines, enzymes), and may be involved in the pathogenesis of CIPN. The mechanisms of CIPN associated with the EVs protein corona can be related with the accumulation of heavy chains of circulating IgG in it. G-class immunoglobulins in EVs are likely to have myelin hydrolyzing, superoxide dismutase, and oxidoreductase enzymatic activities. Moreover, circulating IgG-loaded EVs are a place for complement activation that can lead to membrane attack complex deposition in neuroglia and neurons. The mechanisms of CIPN development that are not associated with IgG in the EVs protein corona are somehow related to the fact that many anticancer drugs induce apoptosis of tumor cells, neurons, and neuroglial cells by various mechanisms. This process may be accompanied by the secretion of EVs with modified cargo (HSPs, 20S proteasomes, miRNAs).

show abstract

“…More recently, the work conducted by Kasimu et al focused on astrocyte-derived exosomes. In their study, the group identified the therapeutic component of these exosomes to be miR-125a-5p (Kasimu et al, 2022). Further pathway analysis found that miR-125a-5p functions by downregulating TRAF6, a key signaling molecule associated with inflammation (Cao et al, 1996;Kasimu et al, 2022) TRAF6 is known to activate NF-lB, which leads to rise of pro-inflammatory cytokines or pathogen-associated molecular patterns, and induce neuropathic pain by activation of JNK/MCP-1 pathway (Lu et al, 2014;Liu et al, 2018).…”

Section: Diabetic Peripheral Neuropathymentioning

confidence: 99%

Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications

Satyadev,

Rivera,

Nikolov

et al. 2023

Front. Physiol.

View full text Add to dashboard Cite

Type 2 diabetes mellitus (T2DM) is one of the most prevalent metabolic disorders worldwide. However, T2DM still remains underdiagnosed and undertreated resulting in poor quality of life and increased morbidity and mortality. Given this ongoing burden, researchers have attempted to locate new therapeutic targets as well as methodologies to identify the disease and its associated complications at an earlier stage. Several studies over the last few decades have identified exosomes, small extracellular vesicles that are released by cells, as pivotal contributors to the pathogenesis of T2DM and its complications. These discoveries suggest the possibility of novel detection and treatment methods. This review provides a comprehensive presentation of exosomes that hold potential as novel biomarkers and therapeutic targets. Additional focus is given to characterizing the role of exosomes in T2DM complications, including diabetic angiopathy, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, diabetic retinopathy, and diabetic wound healing. This study reveals that the utilization of exosomes as diagnostic markers and therapies is a realistic possibility for both T2DM and its complications. However, the majority of the current research is limited to animal models, warranting further investigation of exosomes in clinical trials. This review represents the most extensive and up-to-date exploration of exosomes in relation to T2DM and its complications.

show abstract

miR-125a-5p in astrocytes attenuates peripheral neuropathy in type 2 diabetic mice through targeting TRAF6

Cited by 5 publications

References 29 publications

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

MiR-503-5p alleviates peripheral neuropathy-induced neuropathic pain in T2DM mice by regulating SEPT9 to inhibit astrocyte activation

The Role of Intravesicular Proteins and the Protein Corona of Extracellular Vesicles in the Development of Drug-Induced Polyneuropathy

Exosomes as biomarkers and therapy in type 2 diabetes mellitus and associated complications

Contact Info

Product

Resources

About