Involvement of Transglutaminase-2 in Pathological Changes in Renal Disease

Ikee, Ryota; Kobayashi, Shuzo; Hemmi, Noriaki; Saigusa, Takamitsu; Namikoshi, Tamehachi; Yamada, Muneharu; Imakiire, Toshihiko; Kikuchi, Yasufumi; Suzuki, Shigenobu; Miura, Soichiro

doi:10.1159/000098646

Cited by 31 publications

(30 citation statements)

References 51 publications

(35 reference statements)

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“…We assume the tTG-immunoreactive area in glomeruli of ICGN-E mice did not change because of a lack of mesangial proliferation. In the present study, the tTG-immunoreactivity in the glomeruli of ICGN-T mice decreased because fibrotic change had progressed to terminal sclerosis as in advanced human cases, in which tTG immunoreactivity was weak in fibrous crescents with few cellular components [11]. In summary, the initial increase in tTG in renal tubules was not enhanced by the progress of renal fibrosis in ICGN mice.…”

Section: Discussionsupporting

confidence: 46%

“…These increases occurred in the renal areas showing progressive fibrosis, distinct from the primary lesion causing fibrosis, in a manner similar to the experimental induction models of renal fibrosis. Recently, in renal biopsy specimens from 22 patients with IgA nephropathy (IgAN), a correlation was found between tTG-immunostaining in the mesangial area, and tubulointerstitial changes and glomerular crescents, indicating a relationship between tTG and the formation and progression of renal histopathological changes [11]. Furthermore, tubulointerstitial tTG staining was well correlated with serum creatinine, creatinine clearance, N-acetyl-b-glucosaminidase, urinary b 2 -microglobulin, interstitial fibrosis, and tubular atrophy [11].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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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.

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Section: Discussionsupporting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

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“…Pathological evaluation was performed as previously described [17]. In periodic acid-Schiff-stained sections, the degree of glomerular sclerosis was graded based on the percentage of sclerotic area in each glomerulus [18]: 0 = no sclerosis; 1 = sclerosis involving less than 25% of glomerular surface area; 2 = sclerosis involving 25–50%; 3 = sclerosis involving 50–75%, and 4 = sclerosis involving 75–100%.…”

Section: Methodsmentioning

confidence: 99%

Glucose Metabolism, Insulin Resistance, and Renal Pathology in Non-Diabetic Chronic Kidney Disease

et al. 2008

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Background: The relation between insulin resistance and atherosclerosis is widely recognized, but it remains unknown whether glucose metabolism/insulin resistance is related to renal pathology in humans. Methods: We quantitatively evaluated pathological changes in the glomeruli, tubulointerstitium, and vessels in renal biopsy specimens from 23 patients with non-diabetic chronic kidney disease (CKD), all of whom took a 75-gram oral glucose tolerance test. We correlated the renal pathological changes with fasting plasma glucose (FPG), fasting plasma insulin, 2-hour plasma glucose (2-h PG), 2-hour plasma insulin (2-h PI), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index. Results: HOMA-IR exceeded 1.73 in 11 patients (47.8%), and 2-h PI exceeded 64.0 µU/ml in 14 (60.9%). FPG significantly correlated with interstitial fibrosis (r = 0.532, p = 0.009). The significance was marginal in the correlation between FPG and tubular atrophy and arterio-arteriolosclerosis. Statistically significant correlation was also found between 2-h PG and arterio-arteriolosclerosis (r = 0.422, p = 0.04) and between HOMA-IR and interstitial fibrosis (r = 0.416, p = 0.04). Conclusion: Although precise mechanisms remain unknown, glucose metabolism/insulin resistance seem to play pathogenic roles in formation and progression of renal pathological changes, especially tubulointerstitial and vascular lesions, in non-diabetic CKD.

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“…In a clinical study of 22 patients affected by IgA nephropathy, the most common type of idiopathic glomerulonephritis, TG2 expression correlated with parameters of renal function when an immunohistochemistry approach was used. TG2 staining, predominant in interstitial fibrotic lesions and in proximity to vascular poles, correlated with renal pathology parameters, but it was not related to TGF-beta staining (Ikee et al 2007).…”

Section: Tg2 In Clinical Studies Of Ckdmentioning

confidence: 78%