Inhibition of TGFβ1/Smad pathway by NF-κB induces inflammation leading to poor wound healing in high glucose

Gong, Fan; Zhang, Yun; Cheng, Suoli; Zhou, Xuebing; Zhang, Hanling; Gao, Jian; Li, Xiaoliang; Ma, Guoxu; Wu, Jianke; Zhang, Bowen; Xia, Kun; Zhao, Fei

doi:10.1016/j.cdev.2022.203814

Cited by 7 publications

(2 citation statements)

References 37 publications

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“…TGF‐β/Smad could suppress the NF‐κB signaling by activating the expression of IκBα, which inhibits the nuclear translocation of NF‐κB. On the other hand, NF‐κB could also inhibit the TGF‐β/Smad signaling pathway (Gong et al, 2022). Our result also showed that phosphorylated IκBα was down‐regulated by LPS treatment, and SA could partially reverse it.…”

Section: Discussionmentioning

confidence: 99%

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF‐β/Smad and inhibiting NF‐κB signaling pathway

Wang,

Gao,

Zhang

et al. 2023

Phytotherapy Research

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Osteoarthritis (OA) is a common chronic degenerative disease which is characterized by the disruption of articular cartilage. Syringic acid (SA) is a phenolic compound with anti‐inflammatory, antioxidant, and other effects including promoting osteogenesis. However, the effect of SA on OA has not yet been reported. Therefore, the purpose of our study was to investigate the effect and mechanism of SA on OA in a mouse model of medial meniscal destabilization. The expressions of genes were evaluated by qPCR or western blot or immunofluorescence. RNA‐seq analysis was performed to examine gene transcription alterations in chondrocytes treated with SA. The effect of SA on OA was evaluated using destabilization of the medial meniscus model of mice. We found that SA had no obvious toxic effect on chondrocytes, while promoting the expressions of chondrogenesis‐related marker genes. The results of RNA‐seq analysis showed that extracellular matrix–receptor interaction and transforming growth factor‐β (TGF‐β) signaling pathways were enriched among the up‐regulated genes by SA. Mechanistically, we demonstrated that SA transcriptionally activated Smad3. In addition, we found that SA inhibited the overproduction of lipopolysaccharide‐induced inflammation‐related cytokines including tumor necrosis factor‐α and interleukin‐1β, as well as matrix metalloproteinase 3 and matrix metalloproteinase 13. The cell apoptosis and nuclear factor‐kappa B (NF‐κB) signaling were also inhibited by SA treatment. Most importantly, SA attenuated cartilage degradation in a mouse OA model. Taken together, our study demonstrated that SA could alleviate cartilage degradation in OA by activating the TGF‐β/Smad and inhibiting NF‐κB signaling pathway.

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Section: Discussionmentioning

confidence: 99%

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF‐β/Smad and inhibiting NF‐κB signaling pathway

Wang,

Gao,

Zhang

et al. 2023

Phytotherapy Research

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“…Upon injury and loss of the cutaneous barrier, hemostatic mechanisms are activated including the development of fibrin clots and local vascular constriction [65]. Both surrounding tissue at the injury site and fibrin matrix enhance the pro-inflammatory milieu of the wound through the release of mediators through platelet aggregation such as cytokines and FGF, EGF, TGF-β among others [65][66][67]. Upon adequate hemostasis, blood coagulation provides scaffolds for subsequent infiltrating cells.…”

Section: Fibroblasts' Key Role In Wound Healingmentioning

confidence: 99%

Fibroblasts in Diabetic Foot Ulcers

Voza,

Huerta,

et al. 2024

IJMS

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Fibroblasts are stromal cells ubiquitously distributed in the body of nearly every organ tissue. These cells were previously considered to be “passive cells”, solely responsible for ensuring the turnover of the extracellular matrix (ECM). However, their versatility, including their ability to switch phenotypes in response to tissue injury and dynamic activity in the maintenance of tissue specific homeostasis and integrity have been recently revealed by the innovation of technological tools such as genetically modified mouse models and single cell analysis. These highly plastic and heterogeneous cells equipped with multifaceted functions including the regulation of angiogenesis, inflammation as well as their innate stemness characteristics, play a central role in the delicately regulated process of wound healing. Fibroblast dysregulation underlies many chronic conditions, including cardiovascular diseases, cancer, inflammatory diseases, and diabetes mellitus (DM), which represent the current major causes of morbidity and mortality worldwide. Diabetic foot ulcer (DFU), one of the most severe complications of DM affects 40 to 60 million people. Chronic non-healing DFU wounds expose patients to substantial sequelae including infections, gangrene, amputation, and death. A complete understanding of the pathophysiology of DFU and targeting pathways involved in the dysregulation of fibroblasts are required for the development of innovative new therapeutic treatments, critically needed for these patients.

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Algae-inspired chitosan-pullulan-based multifunctional hydrogel for enhanced wound healing

Liu,

Lei,

et al. 2025

Carbohydrate Polymers

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Inhibition of TGFβ1/Smad pathway by NF-κB induces inflammation leading to poor wound healing in high glucose

Cited by 7 publications

References 37 publications

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF‐β/Smad and inhibiting NF‐κB signaling pathway

Syringic acid promotes cartilage extracellular matrix generation and attenuates osteoarthritic cartilage degradation by activating TGF‐β/Smad and inhibiting NF‐κB signaling pathway

Fibroblasts in Diabetic Foot Ulcers

Algae-inspired chitosan-pullulan-based multifunctional hydrogel for enhanced wound healing

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