Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Paolella, Gaetana; Sposito, Silvia; Romanelli, Antonio Massimiliano; Caputo, Ivana

doi:10.3390/ijms23147513

Cited by 22 publications

(10 citation statements)

References 133 publications

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“…Obstruction of sweat glands and hypohidrosis was reported for patients carrying mutations of TGM1 [38]. Considering the recent advances in the understanding, diagnosis and therapy of TGM-dependent diseases [39][40][41][42][43][44][45][46], it will be interesting to further explore the roles of TGMs in sweat glands and other skin appendages.…”

Section: Discussionmentioning

confidence: 99%

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

Sachslehner

Surbek

Golabi

et al. 2023

IJMS

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The cross-linking of structural proteins is critical for establishing the mechanical stability of the epithelial compartments of the skin and skin appendages. The introduction of isopeptide bonds between glutamine and lysine residues depends on catalysis by transglutaminases and represents the main protein cross-linking mechanism besides the formation of disulfide bonds. Here, we used a fluorescent labeling protocol to localize the activity of transglutaminases on thin sections of the integument and its appendages in mammals and birds. In human tissues, transglutaminase activity was detected in the granular layer of the epidermis, suprabasal layers of the gingival epithelium, the duct of sweat glands, hair follicles and the nail matrix. In the skin appendages of chickens, transglutaminase activity was present in the claw matrix, the feather follicle sheath, the feather sheath and in differentiating keratinocytes of feather barb ridges. During chicken embryogenesis, active transglutaminase was found in the cornifying epidermis, the periderm and the subperiderm. Transglutaminase activity was also detected in the filiform papillae on the tongue of mice and in conical papillae on the tongue of chickens. In summary, our study reveals that transglutaminase activities are widely distributed in integumentary structures and suggests that transglutamination contributes to the cornification of hard skin appendages such as nails and feathers.

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Section: Discussionmentioning

confidence: 99%

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

Sachslehner

Surbek

Golabi

et al. 2023

IJMS

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“…This prevents gluten from reaching the lamina propria and stimulating the immune system ( Varma and Krishnareddy, 2022 ). Other proposed strategies aim at blocking immune response to gluten peptides by: • transglutaminase transglutaminase 2 (TG2) blockers preventing deamidation of gluten peptides and their efficient presentation to CD4 + T cells ( Paolella et al, 2022 ); • inhibiting epithelial damage driven by IL-15 with anti-IL15 antibodies or opposing the outgrowth of malignant IELs in type II refractory CD; • immunotherapy to restore gluten tolerance through stimulation-induced death of small intestinal epithelial cells and immune activation through the production of regulatory T cells ( Cerf-Bensussan and Schuppan, 2021 ; Varma and Krishnareddy, 2022 ). …”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

“…• transglutaminase transglutaminase 2 (TG2) blockers preventing deamidation of gluten peptides and their efficient presentation to CD4 + T cells ( Paolella et al, 2022 );…”

Section: Celiac Disease Novel Therapiesmentioning

confidence: 99%

From an understanding of etiopathogenesis to novel therapies—what is new in the treatment of celiac disease?

Skoracka,

Hryhorowicz,

Tovoli

et al. 2024

Front. Pharmacol.

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Celiac disease, a chronic autoimmune disorder caused by genetic factors and exposure to gluten, is increasingly being recognized and diagnosed in both children and adults. Scientists have been searching for a cure for this disease for many years, but despite the impressive development of knowledge in this field, a gluten-free diet remains the only recommended therapy for all patients. At the same time, the increasing diagnosis of celiac disease in adults, which was considered a childhood disease in the 20th century, has opened a discussion on the etiopathology of the disease, which is proven to be very complex and involves genetic, immunological, nutritional, environmental and gut microbiota-related factors. In this review, we extensively discuss these factors and summarize the knowledge of the proposed state-of-the-art treatments for celiac disease to address the question of whether a better understanding of the etiopathogenesis of celiac disease has opened new directions for therapy.

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“…, 2021 ). However, abnormal regulation of TG is often correlated with pathophysiological conditions, including neurodegenerative diseases ( Wilhelmus et al ., 2014 ), autoimmune conditions, such as coeliac disease ( Paolella et al ., 2022 ), and cancer ( Lee et al ., 2018 ). These pathological conditions are all associated with elevated TG activity; thus, cells modulate rate-limiting levels of catalytically active TG by maintaining the full-length inactive zymogen.…”

Section: Introductionmentioning

confidence: 99%

Fungal transglutaminase domain–containing proteins are involved in hyphal protection at the septal pore against wounding

Mamun,

Maruyama

2023

MBoC

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Transglutaminase (TG) is a ubiquitous enzyme that crosslinks substrates. In humans, TG participates in blood clotting and wound healing. However, the functions related to the cellular protection of microbial TG are unknown. In filamentous fungi, we previously identified SppB, which contains the transglutaminase core (TGc) domain and functions in hyphal protection at the septal pore upon wounding. Here, we further analyzed the cytokinesis-related protein Cyk3 and peptide N-glycanase Png1, as both contain the TGc domain. All three proteins exhibited functional importance in wound-related hyphal protection at the septal pore. Upon wounding, SppB and AoPng1 accumulated at the septal pore, whereas AoCyk3 and AoPng1 normally localized around the septal pore. The putative Cys-His-Asp catalytic triad of SppB is conserved with the human TGc domain-containing kyphoscoliosis peptidase. Catalytic triad disruptive mutants of SppB and AoCyk3 exhibited septal pore plugging defects. Similar to other TGs, SppB underwent wound-induced truncation of the N-terminal region. Notably, TG activity was detected in vivo at the septal pore of wounded hyphae using a fluorescent-labeled substrate; however, the activity was inhibited by the TG inhibitor cystamine. Our study suggests a conserved role for TGc domain-containing proteins in wound-related protection in fungi, similar to that in humans.

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Type 2 Transglutaminase in Coeliac Disease: A Key Player in Pathogenesis, Diagnosis and Therapy

Cited by 22 publications

References 133 publications

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

Transglutaminase Activity Is Conserved in Stratified Epithelia and Skin Appendages of Mammals and Birds

From an understanding of etiopathogenesis to novel therapies—what is new in the treatment of celiac disease?

Fungal transglutaminase domain–containing proteins are involved in hyphal protection at the septal pore against wounding

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