Isozyme-specific Comprehensive Characterization of Transglutaminase-crosslinked Substrates in Kidney Fibrosis

Overview

Journal Sci Rep

Specialty Science

Date 2018 May 11

PMID 29743665

Citations 10

Authors

Hideki Tatsukawa

Risa Otsu

Yuji Tani

Ryosuke Wakita

Kiyotaka Hitomi

Affiliations

Soon will be listed here.

Abstract

Chronic kidney disease is characterized by prolonged decline in renal function, excessive accumulation of ECM, and progressive tissue fibrosis. Transglutaminase (TG) is a crosslinking enzyme that catalyzes the formation of covalent bonds between glutamine and lysine residues, and is involved in the induction of renal fibrosis via the stabilization of ECM and the activation of TGF-β1. Despite the accumulating evidences indicating that TG2 is a key enzyme in fibrosis, genetic knockout of TG2 reduced by only 50% the elevated protein crosslinking and fibrous protein in renal fibrosis model, whereas treatment with TG inhibitor almost completely reduced these levels. Here, we also clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific crosslinked substrates for both TG1 and TG2 in fibrotic kidney. We found that TG1 activity was markedly enhanced in renal tubular epithelium and interstitial areas, whereas TG2 activity increased only in the extracellular space. In total, 47 and 67 possible candidates were identified as TG1 and TG2 substrates, respectively, only in fibrotic kidney. Among them, several possible substrates related to renal disease and fibrosis were identified. These findings provide novel insights into the mechanisms of renal fibrosis through the targeting of isozyme-specific TG substrates.

Citing Articles

Transglutaminase 1: Emerging Functions beyond Skin.

Samani S, Tatsukawa H, Hitomi K, Kaartinen M Int J Mol Sci. 2024; 25(19).

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Development of peptide-based biosensors for detecting cross-linking and deamidation activities of transglutaminases.

Tatsukawa H, Aoyama R, Hitomi K Amino Acids. 2023; 55(6):807-819.

PMID: 37165293 DOI: 10.1007/s00726-023-03272-7.

Tissue transglutaminase exacerbates renal fibrosis via alternative activation of monocyte-derived macrophages.

Shinoda Y, Tatsukawa H, Yonaga A, Wakita R, Takeuchi T, Tsuji T Cell Death Dis. 2023; 14(2):136.

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Inhibiting Transglutaminase 2 Mediates Kidney Fibrosis via Anti-Apoptosis.

Moon J, Choi Y, Kim K, Seo A, Kwon S, Kim Y Biomedicines. 2022; 10(6).

PMID: 35740367 PMC: 9220123. DOI: 10.3390/biomedicines10061345.

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