Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis

Grenard, Pascale; Bresson‐Hadni, Solange; Alaoui, Saı̈d El; Chevallier, M.; Vuitton, Dominique A.; Ricard‐Blum, Sylvie

doi:10.1016/s0168-8278(01)00135-0

Cited by 159 publications

(134 citation statements)

References 30 publications

Supporting

Mentioning

129

Contrasting

Unclassified

Order By: Relevance

“…Perhaps the closest physiological equivalent is in situations of chronic tissue damage, where increased extracellular TG2 both secreted and released by virtue of cell damage leads to increased crosslinking, promoting massive tissue scarring and fibrosis. 9,10,17,19,20 In the present study, the TG2-crosslinked ECM is likely to be composed of TG2 autopolymers, together with heteropolymers of TG2, fibronectin, or other ECM proteins deposited by the coculture system, as shown by Western blotting.…”

Section: Discussionmentioning

confidence: 68%

“…9,10,33 Importantly, in this instance, the enzyme has been used to inhibit tumor growth by a mechanism involving increased stabilization of the ECM, leading to changes in cell behavior that limit tumor invasion and reduce angiogenesis, thus enhancing the host's defense mechanisms. While considerable advances have been made in our understanding of angiogenesis, the development of effective tumor therapeutic strategies that rely on angiogenesis blockade has been less successful when animal studies have been translated into clinical phase trials.…”

Section: Discussionmentioning

confidence: 99%

“…8 However, in a number of different tissues, inappropriate crosslinking of the ECM by TG2 following continuous tissue insult can lead to ECM accumulation and fibrosis. 9,10 Cell surface TG2 is also thought to be involved in cell migration, 11 and cell adhesion, 12 by a mechanism that is independent of its transamidating activity. 13 While some of these proposed functions of TG2 are similar to the critical steps involved in angiogenesis, the role of TG2 in this process is poorly understood.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth

et al. 2005

View full text Add to dashboard Cite

Administration of active TG2 to two different in vitro angiogenesis assays resulted in the accumulation of a complex extracellular matrix (ECM) leading to the suppression of endothelial tube formation without causing cell death. Matrix accumulation was accompanied by a decreased rate of ECM turnover, with increased resistance to matrix metalloproteinase-1. Intratumor injection of TG2 into mice bearing CT26 colon carcinoma tumors demonstrated a reduction in tumor growth, and in some cases tumor regression. In TG2 knockout mice, tumor progression was increased and survival rate reduced compared to wild-type mice. In wild-type mice, an increased presence of TG2 was detectable in the host tissue around the tumor. Analysis of CT26 tumors injected with TG2 revealed fibrotic-like tissue containing increased collagen, TG2-mediated crosslink and reduced organized vasculature. TG2-mediated modulation of cell behavior via changes in the ECM may provide a new approach to solid tumor therapy.

show abstract

Section: Discussionmentioning

confidence: 68%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth

et al. 2005

View full text Add to dashboard Cite

show abstract

“…There are indications that fibrotic processes might be directed by the parasite itself. A parasite trans-glutaminase has been shown to be strongly expressed in and at the border of metacestodes, and this enzyme was capable of cross-linking human collagen in vitro (Grenard et al 2001). Fibrosis itself, in addition to the outer acellular laminated layer, could be responsible for keeping cytolytic immune cells away from the parasite tissue.…”

Section: Alveolar Echinococcosis (Ae)mentioning

confidence: 99%

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

et al. 2007

View full text Add to dashboard Cite

Echinococcus granulosus and Echinococcus multilocularis are cestode parasites, of which the metacestode (larval) stages cause the diseases cystic echinococcosis (CE) and alveolar echinococcosis (AE), respectively. Albendazole and mebendazole are presently used for chemotherapeutical treatment. However, these benzimidazoles do not appear to be parasiticidal in vivo against AE. In addition, failures in drug treatments as well as the occurrence of side-effects have been reported. New drugs are needed to cure AE and CE, which are considered to be neglected diseases. Strategies currently being implemented to identify novel chemotherapeutical treatment options include (i) conventional primary in vitro testing of broad-spectrum anti-infective drugs, either in parallel with, or followed by, animal experimentation ; (ii) studies of drugs which interfere with the proliferation of cancer cells and of Echinococcus metacestodes ; (iii) exploitation of the similarities between the parasite and mammalian signalling machineries, with a special focus on targeting specific signalling receptors ; (iv) in silico approaches, employing the current Echinococcus genomic database information to search for suitable targets for compounds with known modes of action. In the present article, we review the efforts toward obtaining better anti-parasitic compounds which have been undertaken to improve chemotherapeutical treatment of echinococcosis, and summarize the achievements in the field of host-parasite interactions which may also lead to new immuno-therapeutical options.

show abstract

“…In experimental diabetic [25] and non-diabetic renal scarring [15,17], tTG has been proposed as a potential mediator of ECM accumulation. Furthermore, changes in tTg levels have been seen in other types of fibrotic lesions including those affecting the lung [20], liver [7,10], heart [26], and articular cartilage [27].…”

Section: Introductionmentioning

confidence: 99%

Localization of Tissue Transglutaminase (tTG) in Kidney of ICR-Derived Glomerulonephritis (ICGN) Mice

et al. 2009

View full text Add to dashboard Cite

ICR-derived glomerulonephritis (ICGN) mice are a known inbred strain with hereditary nephrotic syndrome and are considered a good animal model of human idiopathic nephrotic syndrome. ICGN mice show proteinuria at a young age, and hypoalbuminemia, hyperlipidemia, anemia and edema accompanies their symptoms with aging. In addition, ICGN mice develop severe anemia with the progression of renal fibrosis similar to human chronic kidney disease (CKD). Recently, tissue transglutaminase (tTG) has been shown to be related to the renal fibrosis in several animal models and CKD patients. In the present study, we investigated the relationship between the progression of renal fibrosis and the localization of tTG in the kidneys using histochemistry and image analysis. Male ICGN mice aged 26-43 weeks were used. They were divided into two groups of early and terminal stages of renal fibrosis, based on plasma levels of blood urea nitrogen (BUN). Normal ICR males aged 11 weeks were used as a control group. tTG was localized to the interstitium in the normal ICR mice. In the early stage of renal fibrosis, the localization of tTG increased in renal tubules showing luminal dilation, as well as in the interstitium; however, the amount of tubular and interstitial tTG decreased in the late stage. In the glomeruli, tTG-immunoreactivity decreased in the late stage of renal fibrosis, despite the progression of glomerular sclerosis. The results suggest that e(g-glutamyl) lysine cross-linking is not directly related to the progression of renal fibrosis in ICGN mice.

show abstract

Transglutaminase-mediated cross-linking is involved in the stabilization of extracellular matrix in human liver fibrosis

Cited by 159 publications

References 30 publications

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth

Matrix changes induced by transglutaminase 2 lead to inhibition of angiogenesis and tumor growth

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

Localization of Tissue Transglutaminase (tTG) in Kidney of ICR-Derived Glomerulonephritis (ICGN) Mice

Contact Info

Product

Resources

About