Inhibition of RAGE by FPS-ZM1 alleviates renal injury in spontaneously hypertensive rats

Liu, Yu; Shen, Wenzhi; Chen, Qi; Cao, Qingxin; Di, Wencheng; Lan, Rongfang; Chen, Zheng; Bai, Jian; Han, Zhonglin; Xu, Wei

doi:10.1016/j.ejphar.2020.173228

Cited by 19 publications

(17 citation statements)

References 39 publications

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“…There was a significant increase in the levels of BUN, Cr, and the 24 h urinary protein compared to that of the control group (p < 0.05). These changes were consistent with previous research results [18]. This indicates that we successfully established a hypertensive nephropathy animal model in the present study.…”

Section: The Effects Of Epa-pl On Serum Parameters and Renal Patholog...supporting

confidence: 94%

“…found that treatments with marine-based n-3 fatty acids (2 g of EPA + DHA (EPA:DHA = 2:1)) had a notably lowering effect on Ang II in the plasma of Chinese hypertensive patients over a treatment period of 90 days [17]. Renin, as an angiotensinogenase, is secreted by the kidneys that participate in the renin-angiotensin system; therefore, the physiological function of the kidney is closely related to the regulation of blood pressure [18]. In the systemic effect on blood pressure regulation, ACE2 can degrade Ang II (vasoconstriction, pro-fibrosis, and pro-inflammation factor), and converts it into Ang (1-7) (vasodialatic and apoptotic factor).…”

Section: The Effects Of Epa-pl On the Renin-angiotensin System In Shrsmentioning

confidence: 99%

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EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways

et al. 2022

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Hypertensive nephropathy is a chronic kidney disease caused by hypertension. Eicosapentaenoic acid (EPA) has been reported to possess an antihypertensive effect, and our previous study suggested that EPA-enriched phospholipid (EPA-PL) had more significant bioactivities compared with traditional EPA. However, the effect of dietary EPA-PL on hypertensive nephropathy has not been studied. The current study was designed to examine the protection of EPA-PL against kidney damage in spontaneously hypertensive rats (SHRs). Treatment with EPA-PL for three weeks significantly reduced blood pressure through regulating the renin–angiotensin system in SHRs. Moreover, dietary EPA-PL distinctly alleviated kidney dysfunction in SHRs, evidenced by reduced plasma creatinine, blood urea nitrogen, and 24 h proteinuria. Histology results revealed that treatment of SHRs with EPA-PL alleviated renal injury and reduced tubulointerstitial fibrosis. Further mechanistic studies indicated that dietary EPA-PL remarkably inhibited the activation of TGF-β and Smad 3, elevated the phosphorylation level of PI3K/AKT, suppressed the activation of NF-κB, reduced the expression of pro-inflammatory cytokines, including IL-1β and IL-6, and repressed the oxidative stress and the mitochondria-mediated apoptotic signaling pathway in the kidney. These results indicate that EPA-PL has potential value in the prevention and alleviation of hypertensive nephropathy.

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Section: The Effects Of Epa-pl On Serum Parameters and Renal Patholog...supporting

confidence: 94%

Section: The Effects Of Epa-pl On the Renin-angiotensin System In Shrsmentioning

confidence: 99%

EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways

et al. 2022

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“…RAGE signaling is also known to play a key role in regulating the renin-angiotensin system (RAS). RAGE has been reported to be protective in models of kidney and cardiac injury caused by hypertension through downregulation of oxidative stress ( 45 ). Clinically, dysregulation of the RAS is evident in critically ill SARS-CoV-2–infected patients ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

Impairing RAGE signaling promotes survival and limits disease pathogenesis following SARS-CoV-2 infection in mice

Jessop¹,

Schwarz²,

Scott³

et al. 2022

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“…FPS-ZM1 is a blood–brain-barrier permeant, tertiary amide compound which is a high-affinity RAGE-specific inhibitor, blocking Aβ binding to the V domain of RAGE [ 27 ]. FPS-ZM1 was often used to inhibit the role of RAGE in an animal experiment [ 28 , 29 ]. Moreover, an inhibitor of JNK, SP600125 [ 20 ], has been widely used.…”

Section: Discussionmentioning

confidence: 99%

Anti-high-mobility group box-1 (HMGB1) mediates the apoptosis of alveolar epithelial cells (AEC) by receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway in the rats of crush injuries

et al. 2022

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Objectives The lung injury is often secondary to severe trauma. In the model of crush syndrome, there may be secondary lung injury. We hypothesize that high-mobility group box 1 (HMGB1), released from muscle tissue, mediates the apoptosis of alveolar epithelial cells (AEC) via HMGB1/Receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway. The study aimed to investigate how HMGB1 mediated the apoptosis of AEC in the rat model. Methods Seventy-five SD male rats were randomly divided into five groups: CS, CS + vehicle, CS + Ethyl pyruvate (EP), CS + FPS-ZM1 group, and CS + SP600125 groups. When the rats CS model were completed after 24 h, the rats were sacrificed. We collected the serum and the whole lung tissues. Inflammatory cytokines were measured in serum samples. Western blot and RT-qPCR were used to quantify the protein and mRNA. Lastly, apoptotic cells were detected by TUNEL. We used SPSS 25.0 for statistical analyses. Results Nine rats died during the experiments. Dead rats were excluded from further analysis. Compared to the CS group, levels of HMGB1 and inflammatory cytokines in serum were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Western blot and RT-qPCR analysis revealed a significant downregulation of HMGB1, RAGE, and phosphorylated-JNK in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups, compared with the CS groups, excluding total-JNK mRNA. Apoptosis of AEC was used TUNEL to assess. We found the TUNEL-positive cells were downregulated in CS + EP, CS + FPS-ZM1, and CS + SP600125 groups. Conclusion The remote lung injury begins early after crush injuries. The HMGB1/RAGE/JNK signaling axis is an attractive target to abrogate the apoptosis of AEC after crush injuries.

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Inhibition of RAGE by FPS-ZM1 alleviates renal injury in spontaneously hypertensive rats

Cited by 19 publications

References 39 publications

EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways

EPA-Enriched Phospholipids Alleviate Renal Interstitial Fibrosis in Spontaneously Hypertensive Rats by Regulating TGF-β Signaling Pathways

Impairing RAGE signaling promotes survival and limits disease pathogenesis following SARS-CoV-2 infection in mice

Anti-high-mobility group box-1 (HMGB1) mediates the apoptosis of alveolar epithelial cells (AEC) by receptor of advanced glycation end-products (RAGE)/c-Jun N-terminal kinase (JNK) pathway in the rats of crush injuries

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