PAPep, a small peptide derived from human pancreatitis-associated protein, attenuates corneal inflammation in vivo and in vitro through the IKKα/β/IκBα/NF–κB signaling pathway

Zhu, Shaopin; Xu, Xun; Liu, Kun; Gu, Qing; Yang, Xiaolu

doi:10.1016/j.phrs.2015.09.013

Cited by 8 publications

(5 citation statements)

References 23 publications

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“…Without stimulation, NF-κB heterodimers bind to IκBα and maintain an inactive form. However, when stimulation occurs, the degradation of IκBα followed by the activation of NF-κB can contribute to the overproduction of proinflammatory cytokines, worsening hepatic damage ( Zhu et al, 2015 ; Shin et al, 2019 ). To confirm this finding, we examined the IκBα and NF-κB protein expression levels in the liver and found that SCU substantially reversed CCl 4 -induced IκBα degradation and NF-κB activation.…”

Section: Discussionmentioning

confidence: 99%

Protective Property of Scutellarin Against Liver Injury Induced by Carbon Tetrachloride in Mice

et al. 2021

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Liver injury is a clinical disorder caused by toxins, drugs, and alcohol stimulation without effective therapeutic approaches thus far. Scutellarin (SCU), isolated from the edible herb Erigeron breviscapus (Vant.) Hand. -Mazz. showed potential hepatoprotective effects, but the mechanisms remain unknown. In this study, transcriptomics combined with nontargeted metabolomics and 16S rRNA amplicon sequencing were performed to elucidate the functional mechanisms of SCU in carbon tetrachloride (CCl4)–induced liver injury in mice. The results showed that SCU exerted potential hepatoprotective effects against CCl4-induced liver injury by repressing CYP2E1 and IκBα/NF-κB signaling pathways, modulating the gut microbiota (especially enriching Lactobacillus), and regulating the endogenous metabolites involved in lipid metabolism and bile acid homeostasis. SCU originates from a functional food that appears to be a promising agent to guard against liver injury.

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Section: Discussionmentioning

confidence: 99%

Protective Property of Scutellarin Against Liver Injury Induced by Carbon Tetrachloride in Mice

et al. 2021

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“…Its overexpression is marked by elevated levels of pancreatitis-associated protein. 18 Our group has previously characterized the promotion by Reg3g of β -cell regeneration and immunosuppression in type 1 diabetes. 14 We also reported that Reg3g accelerated malignant transformation in chronic pancreatitis and promoted pancreatic carcinogenesis partly via immunosuppressive action.…”

Section: Discussionmentioning

confidence: 99%

Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression

et al. 2017

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Reg3g is a potential risk for pancreatic ductal adenocarcinoma (PDAC). We previously demonstrated that Reg3g promoted pancreatic carcinogenesis via a STAT3 signaling pathway in a murine model of chronic pancreatitis. Whether the immune response is involved in tumorigenesis induced by Reg3g remains unknown. In this study, Reg3g-regulated tumor immunity was evaluated in tumor-implanted murine models, immune cells, and tumor microenvironment. In mice that had been orthotopically or ectopically implanted with Panc02 cells, Reg3g overexpression increased EGFR and Ki67, diminished MHC-I and caspase-3 expression, and accelerated growth of tumors. By interacting with PD-1/PD-L1, Reg3g also promoted differentiation of Tregs and recruitment of MDSC, retarded maturation of DCs and inactivation of CD8+ T cells, and suppressed cross-priming of CD8+ T-cell responses by DCs in tumor-bearing mice. Knockdown of Reg3g delayed tumor development in normal mice, but not in CD8+ T-cell-deficient mice. In vitro, Reg3g upregulated EGFR in DCs, activated heme oxygenase-1 (Hmox1) involved JAK2/STAT3 signaling, raised levels of Th2 cytokines in and suppressed maturation of DCs, and enhanced tumor cell proliferation. These results reveal a novel role of Reg3g as an immunosuppressive promoter that weakens tumor-specific antigenicity and suppresses antitumor effects of CD8+ T cells in a murine model of pancreatic cancer. Reg3g produces these effects by activating the JAK2/STAT3 signaling pathway in DCs, triggering the generation of an immunosuppressive tumor microenvironment.

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“…Furthermore, pathological changes in the ocular tissues as a result of inflammation was ameliorated by H-RN, and it exhibited no toxic effects on macrophages and human umbilical vein endothelial cells (HUVECs), and significantly suppressed lipopolysaccharide (LPS)-induced phosphorylation of NF-κB-p65, possibly via the PI3K/Akt signaling pathway (23)(24)(25)(26). Furthermore, other similar functional small peptides have also been identified by our laboratory (27)(28)(29)(30).…”

Section: Introductionmentioning

confidence: 94%

A HGF‑derived peptide suppresses EMT in human lens epithelial cells via the TGF‑β/Smad and Akt/mTOR signaling pathways

et al. 2020

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Posterior capsule opacification (PCO) as a result of proliferation and fibrogenesis of lens epithelial cells (LECs) is the most frequent long-term complication of modern cataract surgery. LECs may undergo epithelial-mesenchymal transition (EMT) that resembles the morphological and molecular characteristics of PCO. A pre-identified novel, hepatocyte growth factor (HGF)-derived peptide H-RN, was reported to exhibit anti-angiogenic activity and anti-inflammatory effects in ocular cells both in vitro and in vivo. However, the role of H-RN in the promotion of the development of EMT in LECs is unknown. In the present study, the effects of H-RN on the development of EMT induced by transforming growth factor (TGF)-β in human LECs, and the possible signaling pathways participating in this process were investigated. The results showed that H-RN promoted the expression of the EMT-associated markers, α-smooth muscle actin and fibronectin, whereas the expression of E-cadherin and connexin 43 were reduced. The morphological changes typically associated with EMT seen in LECs induced by TGF-β2 were inhibited by H-RN, which was consistent with the effects of a TGF-β2 inhibitor, SB431542. Smad2 and Smad3 phosphorylation induced by TGF-β2 were reduced by H-RN, and phosphorylation of Akt, mTOR and P70S6K induced by TGF-β2 were also notably reduced by H-RN in LECs. Therefore, the results of the present study showed that H-RN treatment significantly suppressed the development of EMT induced by TGF-β2, at least partially through the TGF-β/Smad and Akt/mTOR signaling pathways in human LECs. The present study highlights that H-RN, a novel HGF-derived peptide, may be a novel therapeutic agent for prevention and treatment of PCO.

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PAPep, a small peptide derived from human pancreatitis-associated protein, attenuates corneal inflammation in vivo and in vitro through the IKKα/β/IκBα/NF–κB signaling pathway

Cited by 8 publications

References 23 publications

Protective Property of Scutellarin Against Liver Injury Induced by Carbon Tetrachloride in Mice

Protective Property of Scutellarin Against Liver Injury Induced by Carbon Tetrachloride in Mice

Acceleration of pancreatic tumorigenesis under immunosuppressive microenvironment induced by Reg3g overexpression

A HGF‑derived peptide suppresses EMT in human lens epithelial cells via the TGF‑β/Smad and Akt/mTOR signaling pathways

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