Differential expression of multiple transglutaminases in human colon: impaired keratinocyte transglutaminase expression in ulcerative colitis

D'Argenio, G.; Calvani, M.; Valle, N. Della; Cosenza, V.; Di Matteo, G.; Giorgio, P.; Margarucci, S.; Petillo, O.; Jori, F. P.; Galderisi, U.; Peluso, G.
April 2005
Gut;Apr2005, Vol. 54 Issue 4, p496
Academic Journal
Background and aims: Ulcerative colitis (UC) is characterised by refractory inflammatory ulceration and damage to the colon. The mechanisms underlying impaired healing have yet to be defined. As transglutaminase expression resulting in matrix protein cross linking is associated with increased wound healing in a rat model of colitis, we hypothesised that different types of transglutaminase might also play a role in UC. Patients and methods: Endoscopic and histological indices were studied in 26 patients with UC (10 active and 16 inactive) and in 20 normal controls undergoing colonoscopy. Transglutaminase activity was evaluated in plasma (factor XIIIa) by a radioenzymatic method. Factor XIIIa, tissue and keratinocyte transglutaminase protein content, and mRNA expression in the colon were evaluated by western blot analysis and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), respectively. Colonic location of transglutaminases and their reaction products, the ∊-(γ-glutamyl)lysine bonds, was evaluated by immunohistochemistry using specific monoclonal antibodies. Results: Transglutaminase activity was significantly lower in the plasma of patients with active UC (4.2 (2.4) mU/mI; p<0.05 v controls) than in those with inactive UC and controls (10.6 (2.2) and 12.1 (1.7) mU/mI). As shown by western blot, protein levels of tissue transglutaminase and factor XIIIa were unchanged in active UC compared with inactive disease and controls, while the keratinocyte form was reduced in active UC. Tissue transglutaminase and factor XIIIa immunostaining was strongly present in damaged areas colocalising with isopeptide bonds. In contrast, the keratinocyte form was almost absent in active UC and localised in the upper part of the crypts in normal subjects. RT-PCR showed upregulation of tissue transglutaminase mRNA in active UC (320% compared with controls) while keratinocyte transglutaminase gene expression was downregulated in active UC. Conclusions: The results of the present study support the concept that, in the damaged colon, transglutaminases are needed in response to chronic injury and underline the key role of these enzymes in mucosal healing.


Related Articles

  • Modulation of Cellular Cholesterol and Its Effect on Cornified Envelope Formation in Cultured Human Epidermal Keratinocytes. Schmidt, Rainer; Parish, Edward J.; Dionisius, Veronique; Cathelineau, Christine; Michel, Serge; Shroot, Braham; Rolland, Alain; Brzokewicz, Alain; Reichert, Uwe // Journal of Investigative Dermatology;Nov91, Vol. 97 Issue 5, p771 

    When cultured human epidermal keratinocytes (NHK) reach confluence they start to differentiate and an increase in the total cellular cholesterol content is observed. This increase parallels the appearance of a characteristic feature of terminal keratinocyte differentiation, the spontaneous...

  • E2F suppression and Sp1 overexpression are sufficient to induce the differentiation-specific marker, transglutaminase type 1, in a squamous cell carcinoma cell line. Chung Fai Wong; Barnes, Liam M.; Dahler, Alison L.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A. // Oncogene;5/12/2005, Vol. 24 Issue 21, p3525 

    Recently, E2F function has expanded to include the regulation of differentiation in human epidermal keratinocytes (HEKs). We extend these findings to report that in HEKs, Sp1 is a differentiation-specific activator and a downstream target of E2F-mediated suppression of the...

  • Transglutaminases: new target molecules for inflammatory bowel disease? Siegmund, B.; Zeitz, M. // Gut;Apr2005, Vol. 54 Issue 4, p443 

    This article presents information on transglutarninases. The family of transglutaminases (TG) includes the plasma form factor XIIIa as well as the tissue transglutaminase (tTG) and keratinocyte transglutaminase (TGk). In particular, tTG reminds every gastroenterologist primarily of coeliac...

  • Transglutaminase Function in Epidermis. Eckert, Richard L.; Sturniolo, Michael T.; Broome, Ann-Marie; Ruse, Monica; Rorke, Ellen A. // Journal of Investigative Dermatology;Mar2005, Vol. 124 Issue 3, p481 

    Surface epithelial cells, such as the epidermal keratinocyte, undergo a process of terminal cell differentiation that results in the construction of a multilayered epithelium. This epithelium functions to protect the organism from the environment. Transglutaminases, enzymes that catalyze the...

  • Potential Role for High and Low Molecular Weight Tissue Transglutaminases in Transforming Mammalian Cell Properties. Mezzogiorno, A.; Esposito, V. // Current Drug Targets - Immune, Endocrine & Metabolic Disorders;Nov2001, Vol. 1 Issue 3, p223 

    Tissue transglutaminase (tTGase, tTG) is known as being implicated in the intracellular cross-linking of proteins occurring in a growing series of physiological conditions including - just to mention the most relevant ones- programmed cell death (apoptosis), cell adhesion, growth, spreading and...

  • Transglutaminases in Normal and Transformed Human Keratinocytes in Culture. Schmidt, Rainer; Michel, Serge; Shroot, Braham; Reichert, Uwe // Journal of Investigative Dermatology;Apr88, Vol. 90 Issue 4, p475 

    The transglutaminases of cultured normal and transformed human keratinocytes (line SV-K14) are characterized. Both cell types display two forms of the enzyme, one of which is cytosoluble (TGc) and the other which is associated with the plasma membrane (TGm). Normal keratinocytes contain...

  • Inhibition of Human Epidermal Transglutaminases In Vitro and In Vivo by Tyrosinamidomethyl Dihydrohaloisoxazoles. Goldsmith, Lowell A.; DeYoung, Larry M.; Falciano, Vincent; Ballaron, Stephen J.; Akers, William // Journal of Investigative Dermatology;Jul91, Vol. 97 Issue 1, p156 

    Tyrosinamidomethyl dihydrohaloisoxazoles (THX) irreversibly inhibit isolated epidermal transglutaminases and ionophore-induced cell envelope formation in malignant human keratinocytes. In cultured human foreskin keratinocytes cultured in 10-5 M THX for 5 days, soluble and particulate...

  • Increased Cholesterol Sulfate and Cholesterol Sulfotransferase Activity in Relation to the Multi-step Process of Differentiation in Human Epidermal Keratinocytes. Jetten, Anton M.; George, Margaret A.; Nervi, Clara; Boone, Lawrence R.; Rearick, James I. // Journal of Investigative Dermatology;Feb89, Vol. 92 Issue 2, p203 

    In this study the synthesis of cholesterol sulfate is examined in relation to the process of squamous differentiation in normal human epidermal keratinocytes (NHEK) in culture. During the exponential growth phase, NHEK cells exhibit a relatively high colony-forming efficiency and appear...

  • Effects of THz Exposure on Human Primary Keratinocyte Differentiation and Viability. Clothier, R.H.; Bourne, N. // Journal of Biological Physics;Apr2003, Vol. 29 Issue 2/3, p179 

    Primary human keratinocytes can be driven, in vitro, to differentiate, via activation of transglutaminases, by raising the culture medium calcium concentration above 1 mM. This results in transglutaminase regulated cross linking of specific amino acids with resultant cornified envelope...


Read the Article


Sign out of this library

Other Topics