Identification and characterization of substrates crosslinked by transglutaminases in liver and kidney fibrosis

Tatsukawa, Hideki; Takeuchi, Taishu; Shinoda, Yoshiki; Hitomi, Kiyotaka

doi:10.1016/j.ab.2020.113629

Cited by 8 publications

(6 citation statements)

References 24 publications

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“…It is known that TG2 regulates several physiological processes, including cell differentiation, inflammation, fibrosis and apoptosis [3][4][5][6]. Consequently, alterations in the activity of TG2 can have a role in the pathogenesis of several chronic disorders such as inflammatory bowel disease, liver disease, and liver and kidney fibrosis [7,24].…”

Section: Discussionmentioning

confidence: 99%

Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis

Riezzo

Orlando

Clemente

et al. 2021

ARCH BIOL SCI BELGRA

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Since tissue transglutaminase-2 (TG2) can represent a marker of inflammation for some gastrointestinal (GI) diseases, we aimed to evaluate TG2 and inflammatory markers? mucosal content in gastric antrum biopsies to shed light on the histological and biochemical background of chronic gastritis inflammation. Fifty-one of 78 patients who underwent upper GI endoscopy (UGIE) for dyspeptic symptoms, had a gastric biopsy. The symptom profile was assessed by a GI symptom rating scale (GSRS) score. Thirtyfive patients (69%) showed chronic gastritis. TG2, interleukin-6 (IL)-6, IL-8, IL-10, tumor necrosis factor (TNF)-?, lipopolysaccharides (LPS) and toll-like receptor (TLR)-4 were evaluated in serum and the culture medium of gastric biopsies. TG2, IL-8, IL-10, TLR-4 and TNF-? were significantly higher in active chronic gastritis than in the inactive one and were linked to macrophage concentration. IL-6 was significantly lower in the active form of chronic gastritis than in the inactive one and negatively correlated with TG2. Lastly, IL- 10 significantly correlated with the macrophage score. TG2 can exert an active role in chronic gastritis pathogenesis by cooperating with different markers of inflammation. It seems that TG2 can represent a possible therapeutic target for modulating inflammation and disease progression.

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Section: Discussionmentioning

confidence: 99%

Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis

Riezzo

Orlando

Clemente

et al. 2021

ARCH BIOL SCI BELGRA

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“…These enzymes regulate a crosslinking reaction between glutamine and lysine residues ( Figure 2 ) [ 13 , 26 ]. Importantly, TG activity is not limited to crosslinking, and TGs have a number of different substrates [ 13 , 27 ]. TGs also serve as scaffolding proteins important for basic cell functions, including cell adhesion and signal transduction [ 26 , 28 ].…”

Section: Ecm Crosslinking Biochemical Pathwaysmentioning

confidence: 99%

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Lloyd,

2024

Cells

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The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications to ECM proteins such as collagens alter ECM structure and function. Dysregulation of crosslinking enzymes as well as changes in crosslinking composition are prevalent in fibrosis. Because of the crucial roles these ECM crosslinking pathways play in disease, the enzymes that govern crosslinking events are being explored as therapeutic targets for fibrosis. Here, we review in depth the molecular mechanisms underlying ECM crosslinking, how ECM crosslinking contributes to fibrosis, and the therapeutic strategies being explored to target ECM crosslinking in fibrosis to restore normal tissue structure and function.

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“…These enzymes regulate a crosslinking reaction between glutamine and lysine residues (Figure 2) [15,28]. Importantly, TG activity is not limited to crosslinking and TGs have a number of different substrates [15,29]. TGs also serve as scaffolding proteins important for basic cell functions including cell adhesion and signal transduction [28,30].…”

Section: Transglutaminase (Tg) Crosslinkingmentioning

confidence: 99%

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Lloyd,

2024

Preprint

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The extracellular matrix (ECM) provides structural support for tissues and regulatory signals for resident cells. ECM requires a careful balance between protein accumulation and degradation for homeostasis. Disruption of this balance can lead to pathological processes such as fibrosis in organs across the body. Post-translational crosslinking modifications to ECM proteins such as collagens alter ECM structure and function. Dysregulation of crosslinking enzymes as well as changes in crosslinking composition are prevalent in fibrosis. Because of the crucial roles that ECM crosslinking pathways play in disease, the enzymes that govern crosslinking events are being explored as therapeutic targets for fibrosis. Here we review in-depth the molecular mechanisms underlying ECM crosslinking, how ECM crosslinking contributes to fibrosis, and therapeutic strategies being explored to target ECM crosslinking in fibrosis to restore normal tissue structure and function.

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Identification and characterization of substrates crosslinked by transglutaminases in liver and kidney fibrosis

Cited by 8 publications

References 24 publications

Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis

Tissue transglutaminase is involved in the inflammatory processes of active chronic gastritis

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

Exploring Extracellular Matrix Crosslinking as a Therapeutic Approach to Fibrosis

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