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. 2023 Jul;50(7):5991-6003.
doi: 10.1007/s11033-023-08544-9. Epub 2023 Jun 3.

Angiotensin-(1-7) ameliorates intestinal barrier dysfunction by activating the Keap1/Nrf2/HO-1 signaling pathway in acute pancreatitis

Ruru Gu  1 , Tianyu Cui  1 , Yinan Guo  1 , Yingyi Luan  1 , Xueran Wang  1 , Ruixia Liu #  1 , Chenghong Yin #  2
Affiliations

Angiotensin-(1-7) ameliorates intestinal barrier dysfunction by activating the Keap1/Nrf2/HO-1 signaling pathway in acute pancreatitis

Ruru Gu et al. Mol Biol Rep. 2023 Jul.

Abstract

Background: Intestinal barrier dysfunction is a serious complication associated with acute pancreatitis (AP). Angiotensin (Ang)-(1-7) plays a protective role in the intestinal barrier, but the underlying mechanism remains clear. This study investigated the impact of Ang-(1-7) on AP-induced intestinal dysfunction and its involvement in the Keap1/Nrf2/HO-1 pathway.

Methods and results: We studied caerulein- and lipopolysaccharide (LPS)-induced AP in mice and an epithelial cell line (IEC-6) from the small intestinal crypt of rats. Ang-(1-7) was administered orally or via the tail vein. IEC-6 cells were divided into five groups: control; LPS; LPS + Ang-(1-7); LPS + Ang-(1-7) + ML385 (an Nrf2 inhibitor); and LPS + ML385. Pancreatic and intestinal histopathology scores were analyzed using the Schmidt and Chiu scores. The expression of intestinal barrier-associated proteins and Keap1/Nrf2/HO-1 pathway constituents was assessed by RT-PCR and western blotting. The peroxide and antioxidant activities in the IEC-6 cells were measured. Compared to those in AP mice, Ang-(1-7) diminished the intestinal levels of proinflammatory factors (interleukin-1β and tumor necrosis factor α) and serum levels of intestine permeability (D-lactate). Ang-(1-7) increased the expression of barrier-associated proteins (aquaporin-1, claudin-1, and occludin) compared to those in the AP and LPS group. Moreover, Ang-(1-7) promoted the Keap/Nrf2/HO-1 pathway, which resulted in significantly reduced malondialdehyde and increased superoxide dismutase levels.. However, ML385 abolished the effects of Ang-(1-7) on barrier-associated proteins and reversed the Keap1/Nrf2/HO-1 pathway.

Conclusions: Ang-(1-7) reduces AP-induced intestinal inflammation and oxidative injuries by activating the Keap1/Nrf2/HO-1 pathway.

Keywords: Acute pancreatitis; Ang-(1–7); Intestinal barrier; Intestinal inflammation; Oxidative stress.

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References

    1. Petrov MS, Yadav D (2019) Global epidemiology and holistic prevention of pancreatitis. Nat Rev Gastroenterol Hepatol 16(3):175–184. https://doi.org/10.1038/s41575-018-0087-5 - DOI - PubMed - PMC
    1. Boxhoorn L, Voermans RP, Bouwense SA et al (2020) Acute pancreatitis. Lancet 396(10252):726–734. https://doi.org/10.1016/S0140-6736(20)31310-6 - DOI - PubMed
    1. Wei B, Wu Q, Yang X, Lai C, Su Z (2022) Liang Z (2022) Effect of TRAF6 in acute pancreatitis-induced intestinal barrier injury via TLR4/NF-κB signal pathway. Tissue Cell. 76:101792. https://doi.org/10.1016/j.tice.2022.101792 - DOI - PubMed
    1. Agarwala R, Rana SS, Sharma R et al (2020) Gastrointestinal failure is a predictor of poor outcome in patients with acute pancreatitis. Dig Dis Sci 65(8):2419–2426. https://doi.org/10.1007/s10620-019-05952-5 - DOI - PubMed
    1. Scaldaferri F, Pizzoferrato M, Gerardi V et al (2012) The gut barrier: new acquisitions and therapeutic approaches. J Clin Gastroenterol 46(Suppl):S12–S17. https://doi.org/10.1097/MCG.0b013e31826ae849 - DOI - PubMed

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