Stimulator of interferon genes/Interferon regulatory factor 3 (STING-IRF3) and inflammasome-activation mediated pyroptosis biomarkers: a network of integrated pathways in diabetic nephropathy

干扰素基因刺激物/干扰素调节因子 3 (STING-IRF3) 和炎症小体活化介导的细胞焦亡生物标志物:糖尿病肾病中的综合通路网络

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作者:Omnia Safwat El-Deeb, Yasser Mostafa Hafez, Amira Kamel Eltokhy, Marwa Mahmoud Awad, Rehab Ahmed Ahmed El-Shaer, Muhammad Tarek Abdel Ghafar, Marwa Mohamed Atef

Background

Diabetic Nephropathy (DN) is serious diabetic complication affecting the structure and function of the kidney. This study assessed the stimulator of interferon genes/ Interferon regulatory factor 3 (STING/IRF3) signaling pathway roles and inflammasome-activation mediated pyroptosis, being imperative pathways of inordinate importance in disease progression, in DN throughout its different stages.

Conclusion

The study documented the forthcoming role of STING in DN progression and its positive correlation with inflammasome-activation mediated pyroptosis biomarkers throughout its three different stages; launching new horizons in DN pathogenesis by highlighting its role as a reliable prognostic biomarker.

Methods

45 Diabetic cases were categorized into three groups based on their albuminuric status as follow: Normoalbuminuric, Microalbuminuric and Macroalbuminuric diabetic groups and 15 healthy subjects as controls were included. We evaluated STING and absent in melanoma 2 (AIM2) messenger RNA (mRNA) expressions from whole blood using quantitative RT-PCR. Additionally, Serum levels of STING, AIM2, IRF3, Nod like receptor pyrins-3 (NLRP3), interleukin-1β (IL-1β) and caspase-1 were assessed by ELISA technique.

Results

The study documented that STING and AIM2 mRNA expressions had significantly increased in DN cases with highest value in macroalbuminuric diabetic groups (p < 0.001*). Parallel results were observed concerning serum STING, AIM2, IRF3, NLRP3, Caspase-1 in addition to IL-1β levels (p < 0.001*).

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