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Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Autophagy of macrophages is regulated by PI3k/Akt/mTOR signalling in the development of diabetic encephalopathy
Beiyun Wang1, Yuan Zhong1, Qinjie Li1
1Department of Gerontology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Abstract:
The development of diabetic encephalopathy (DE) is enhanced by inflammatory macrophages, and is suppressed by macrophage autophagy. However, the molecular signaling that controls macrophage autophagy in DE remains ill-defined. Here, DE is induced in rats that received intraperitoneal injection of streptozotocin (STZ). In macrophages isolated from the brain of the rats, we detected downregulated autophagy activity and enhanced PI3k/Akt/mTOR/S6K1 signaling. In order to examine the role of autophagy and PI3k/Akt/mTOR signaling in DE development, an mTOR inhibitor, rapamycin, or an autophagy inhibitor, chloroquine (CQ), were administered to the rats that that received STZ. We found that rapamycin significantly enhanced DE development through mTOR suppression-induced augmentation of macrophage autophagy, while CQ significantly decreased DE development through suppression of macrophage autophagy. Together, our data suggest that PI3k/Akt/mTOR signaling may promote the development of DE through suppression of macrophage autophagy.
Insights
Diabetic encephalopathy (DE) involves brain inflammation. PI3k/Akt/mTOR signaling suppresses macrophage autophagy, worsening DE, while inhibiting this pathway may protect against DE.
Area of Science:
- Neuroscience
- Cell Biology
- Endocrinology
Background:
- Diabetic encephalopathy (DE) is a complication of diabetes, characterized by cognitive decline.
- Inflammatory macrophages exacerbate DE, whereas macrophage autophagy plays a protective role.
- The precise molecular mechanisms regulating macrophage autophagy in DE are not fully understood.
Purpose of the Study:
- To investigate the role of the PI3k/Akt/mTOR/S6K1 signaling pathway in regulating macrophage autophagy during diabetic encephalopathy.
- To determine the therapeutic potential of modulating this pathway in DE.
Main Methods:
- Diabetic encephalopathy was induced in rats using streptozotocin (STZ).
- Macrophage autophagy activity and PI3k/Akt/mTOR/S6K1 signaling were assessed in brain tissue.
- Rats were treated with an mTOR inhibitor (rapamycin) or an autophagy inhibitor (chloroquine, CQ) to evaluate their effects on DE.
Main Results:
- Downregulated autophagy and enhanced PI3k/Akt/mTOR/S6K1 signaling were observed in macrophages from STZ-induced diabetic rats.
- Rapamycin treatment, by inhibiting mTOR, enhanced macrophage autophagy and significantly worsened DE.
- Chloroquine treatment, by inhibiting autophagy, significantly decreased DE development.
Conclusions:
- The PI3k/Akt/mTOR/S6K1 signaling pathway appears to promote diabetic encephalopathy by suppressing macrophage autophagy.
- Targeting this pathway, specifically by enhancing macrophage autophagy, may offer a therapeutic strategy for managing DE.
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