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MicroRNA In situ Hybridization for Formalin Fixed Kidney Tissues
Published on: November 30, 2013
MicroRNA‑24 attenuates diabetic vascular remodeling by suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway
Zhixing Fan1, Jian Yang2, Chaojun Yang3
1Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China.
Abstract:
Vascular remodeling plays an important role in the pathogenesis of diabetic cardiovascular complications. Previous published research has indicated that microRNA‑24 (miR‑24) is involved in diabetic vascular remodeling, but the underlying molecular mechanisms have yet to be fully elucidated. The aim of the present study was to investigate whether adenovirus‑mediated miR‑24 overexpression can suppress the NOD‑like receptor family pyrin domain‑containing 3 (NLRP3)‑related inflammatory signaling pathway and attenuate diabetic vascular remodeling. The carotid arteries of diabetic rats were harvested and prepared for analysis. Reverse transcription‑quantitative PCR and western blotting assays were used to detect the expressions of related mRNAs and proteins. Morphological examinations, including hematoxylin and eosin, immunohistochemical and Masson's trichrome staining, were also performed. The results of the present study demonstrated that miR‑24 upregulation suppressed neointimal hyperplasia and accelerated reendothelialization in the injured arteries, lowered the expression of NLRP3, apoptosis‑associated speck‑like protein, caspase‑1, proliferating cell nuclear antigen, CD45, interleukin (IL)‑1β, IL‑18 and tumor necrosis factor‑α, and increased the expression of CD31, smooth muscle (SM) α‑actin and SM‑myosin heavy chain. These data indicated that miR‑24 overexpression can attenuate vascular remodeling in a diabetic rat model through suppressing the NLRP3/caspase‑1/IL‑1β signaling pathway.
Insights
MicroRNA-24 (miR-24) overexpression suppresses inflammation and vascular remodeling in diabetic rats. This study shows miR-24 attenuates diabetic cardiovascular complications by inhibiting the NLRP3 inflammasome pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Endocrinology
Background:
- Diabetic cardiovascular complications are linked to vascular remodeling.
- MicroRNA-24 (miR-24) is implicated in diabetic vascular remodeling, but mechanisms are unclear.
- The NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome pathway is a potential target.
Purpose of the Study:
- To investigate if miR-24 overexpression suppresses the NLRP3 inflammasome pathway.
- To determine if miR-24 attenuates diabetic vascular remodeling in a rat model.
Main Methods:
- Adenovirus-mediated miR-24 overexpression in diabetic rat carotid arteries.
- Reverse transcription-quantitative PCR and western blotting for gene and protein expression.
- Histological analyses (H&E, immunohistochemistry, Masson's trichrome staining).
Main Results:
- miR-24 upregulation reduced neointimal hyperplasia and enhanced reendothelialization.
- miR-24 suppressed NLRP3, caspase-1, IL-1β, IL-18, TNF-α, PCNA, and CD45 expression.
- miR-24 increased CD31, smooth muscle α-actin, and SM-myosin heavy chain expression.
Conclusions:
- miR-24 overexpression attenuates vascular remodeling in diabetic rats.
- The mechanism involves the suppression of the NLRP3/caspase-1/IL-1β signaling pathway.
- miR-24 is a potential therapeutic target for diabetic vascular complications.
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