Efficacy and safety of erythropoietin in a chronic model of Inflammatory Bowel Disease

Silva, Inês; Estarreja, João; Pinto, Rui; Mateus, Vanessa

doi:10.1016/j.biopha.2022.113944

Cited by 2 publications

(2 citation statements)

References 34 publications

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“…The long-term use of conventional medical treatment 5-aminosalicylic acid drugs, glucocorticoids and immunosuppressants caused a variety of adverse reactions, and reduced the quality of life of patients. ( 4 ) Therefore, identifying a potential therapeutic target for IBD has become a priority in the recent research.…”

Section: Introductionmentioning

confidence: 99%

Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress

Qin,

Chu,

Ding

et al. 2024

J. Clin. Biochem. Nutr.

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Sirtuin 3 involved in development of various diseases, but its role in inflammatory bowel disease is still unknown. We used inflammatory bowel disease biopsies, colitis animal model, and vitro cells RAW264.7 to study the role of Sirtuin 3 in the pathophysiology of inflammatory bowel disease. Sirtuin 3 negatively correlated with intestinal TNF-α. Sirt3 was less pronounced in pediatric and adult inflammatory bowel disease patients compared with corresponding control group. Sirtuin 3 activator Honokiol suppressed dextran sulfate sodium induced colonic manifestations, while Sirt3 inhibitor caused opposite results. Honokiol inhibited colonic oxidative stress by and reduced intestinal permeability. Honokiol repressed inflammatory response by reducing macrophage infiltration, pro-inflammatory cytokines TNF-α, IL-1β, and IL-6 levels, and inhibiting activation of NF-κB p65 in the colitis mice. However, Sirt3 inhibitor amplified colonic oxidative stress and inflammatory response. In vitro study, Sirt3 inhibitor or siRNA Sirtuin 3 activated NF-κB p65 and enhanced TNF-α, IL-1β, and IL-6 secretion from LPS stimulated RAW264.7, while Honokiol remarkably attenuated these pro-inflammatory cytokines secretion. Finally, knockdown of Sirt3 in Caco-2 cells enhanced TNF-α induced intestinal barrier integrity injury. Sirtuin 3 negatively regulates inflammatory bowel disease progression via reducing colonic inflammation and oxidative stress. Sirtuin 3 is a promising therapeutic target in clinical application for inflammatory bowel disease therapy.

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Section: Introductionmentioning

confidence: 99%

Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress

Qin,

Chu,

Ding

et al. 2024

J. Clin. Biochem. Nutr.

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“…Erythropoietin (EPO) is a U.S. Food and Drug Administration (FDA) approved drug for the treatment of anemia associated with chronic kidney disease. The functional role of EPO via EPO receptors (EPOR) has been reported in many other tissues including the intestine [ 8 – 10 ]. Our recent study has shown a novel beneficial effect of EPO against POI by reducing oxidative stress and inflammatory insults in wild-type mice [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility

et al. 2023

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Background Dysmotility and postoperative ileus (POI) are frequent major clinical problems post-abdominal surgery. Erythropoietin (EPO) is a multifunctional tissue-protective cytokine that promotes recovery of the intestine in various injury models. While EPO receptors (EPOR) are present in vagal Schwann cells, the role of EPOR in POI recovery is unknown because of the lack of EPOR antagonists or Schwann-cell specific EPOR knockout animals. This study was designed to explore the effect of EPO via EPOR in vagal nerve Schwann cells in a mouse model of POI. Results The structural features of EPOR and its activation by EPO-mediated dimerization were understood using structural analysis. Later, using the Cre-loxP system, we developed a myelin protein zero (Mpz) promoter-driven knockout mouse model of Schwann cell EPOR (MpzCre-EPORflox/flox / Mpz-EPOR-KO) confirmed using PCR and qRT-PCR techniques. We then measured the intestinal transit time (ITT) at baseline and after induction of POI with and without EPO treatment. Although we have previously shown that EPO accelerates functional recovery in POI in wild type mice, EPO treatment did not improve functional recovery of ITT in POI of Mpz-EPOR-KO mice. Conclusions To the best of our knowledge, this is the first pre-clinical study to demonstrate a novel mouse model of EPOR specific knock out on Schwan cells with an effect in the gut. We also showed novel beneficial effects of EPO through vagus nerve Schwann cell-EPOR in intestinal dysmotility. Our findings suggest that EPO-EPOR signaling in the vagus nerve after POI is important for the functional recovery of ITT.

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Efficacy and safety of erythropoietin in a chronic model of Inflammatory Bowel Disease

Cited by 2 publications

References 34 publications

Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress

Sirtuin 3 ameliorates inflammatory bowel disease via inhibiting intestinal inflammation and oxidative stress

A critical role for erythropoietin on vagus nerve Schwann cells in intestinal motility

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