Transglutaminase 2 as a novel target in chronic kidney disease - Methods, mechanisms and pharmacological inhibition

source extracted confidence: high 2026-04-09
#animals #fibrosis #humans #protein-glutamine-gamma-glutamyltransferase-2 #renal-insufficiency-chronic

Transglutaminase 2 as a novel target in chronic kidney disease - Methods, mechanisms and pharmacological inhibition

Prat-Duran et al., 2021 | Pharmacol Ther | Systematic Review

Citation

Prat-Duran Judit, Pinilla Estéfano, ... Buus Niels Henrik. Transglutaminase 2 as a novel target in chronic kidney disease - Methods, mechanisms and pharmacological inhibition. Pharmacol Ther. 2021-Jun;222:107787. doi:10.1016/j.pharmthera.2020.107787

Abstract

Chronic kidney disease (CKD) is a global health problem with a prevalence of 10-15%. Progressive fibrosis of the renal tissue is a main feature of CKD, but current treatment strategies are relatively unspecific and delay, but do not prevent, CKD. Exploration of novel pharmacological targets to inhibit fibrosis development are therefore important. Transglutaminase 2 (TG2) is known to be central for extracellular collagenous matrix formation, but TG2 is a multifunctional enzyme and novel research has broadened our view on its extra- and intracellular actions. TG2 exists in two conformational states with different catalytic properties as determined by substrate availability and local calcium concentrations. The open conformation of TG2 depends on calcium and has transamidase activity, central for protein modification and cross-linking of extracellular protein components, while the closed conformation is a GTPase involved in transmembrane signaling processes. We first describe different methodologies to assess TG2 activity in renal tissue and cell cultures such as biotin cadaverine incorporation. Then we systematically review animal CKD models and preliminary studies in humans (with diabetic, IgA- and chronic allograft nephropathy) to reveal the role of TG2 in renal fibrosis. Mechanisms behind TG2 activation, TG2 externalization dependent on Syndecan-4 and interactions between TG and profibrotic molecules including transforming growth factor β and the angiotensin II receptor are discussed. Pharmacological TG2 inhibition shows antifibrotic effects in CKD. However, the translation of TG2 inhibition to treat CKD in patients is a challenge as clinical information is limited, and further studies on pharmacokinetics and efficacy of the individual compounds are required.

Key Findings

However, the translation of TG2 inhibition to treat CKD in patients is a challenge as clinical information is limited, and further studies on pharmacokinetics and efficacy of the individual compounds are required.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size See abstract
Age Range See abstract
Condition See abstract

MeSH Terms

  • Animals
  • Fibrosis
  • Humans
  • Protein Glutamine gamma Glutamyltransferase 2
  • Renal Insufficiency, Chronic

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Research Support, Non-U.S. Gov't, Systematic Review
  • Vertical: biotin

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09