Endoplasmic Reticulum-Associated Biomarkers for Molecular Phenotyping of Rare Kidney Disease

Int J Mol Sci. 2021 Feb 22;22(4):2161. doi: 10.3390/ijms22042161.

Abstract

The endoplasmic reticulum (ER) is the central site for folding, post-translational modifications, and transport of secretory and membrane proteins. An imbalance between the load of misfolded proteins and the folding capacity of the ER causes ER stress and an unfolded protein response. Emerging evidence has shown that ER stress or the derangement of ER proteostasis contributes to the development and progression of a variety of glomerular and tubular diseases. This review gives a comprehensive summary of studies that have elucidated the role of the three ER stress signaling pathways, including inositol-requiring enzyme 1 (IRE1), protein kinase R-like ER kinase (PERK), and activating transcription factor 6 (ATF6) signaling in the pathogenesis of kidney disease. In addition, we highlight the recent discovery of ER-associated biomarkers, including MANF, ERdj3, ERdj4, CRELD2, PDIA3, and angiogenin. The implementation of these novel biomarkers may accelerate early diagnosis and therapeutic intervention in rare kidney disease.

Keywords: biomarkers; endoplasmic reticulum; kidney disease.

Publication types

  • Review

MeSH terms

  • Activating Transcription Factor 4 / genetics
  • Activating Transcription Factor 4 / metabolism
  • Animals
  • Biomarkers / analysis
  • Biomarkers / metabolism*
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism
  • Disease Models, Animal
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress / physiology
  • Endoribonucleases / metabolism
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • HSP40 Heat-Shock Proteins / metabolism
  • Humans
  • Kidney Diseases / metabolism*
  • Molecular Chaperones / metabolism
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Protein Disulfide-Isomerases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Transcription Factor CHOP / metabolism
  • X-Box Binding Protein 1 / metabolism
  • eIF-2 Kinase / genetics
  • eIF-2 Kinase / metabolism

Substances

  • ATF4 protein, human
  • Biomarkers
  • CRELD2 protein, human
  • Cell Adhesion Molecules
  • DDIT3 protein, human
  • DNAJB11 protein, human
  • Extracellular Matrix Proteins
  • HSP40 Heat-Shock Proteins
  • MANF protein, human
  • Molecular Chaperones
  • Nerve Growth Factors
  • X-Box Binding Protein 1
  • XBP1 protein, human
  • Activating Transcription Factor 4
  • Transcription Factor CHOP
  • EIF2AK3 protein, human
  • ERN1 protein, human
  • Protein Serine-Threonine Kinases
  • eIF-2 Kinase
  • Endoribonucleases
  • Protein Disulfide-Isomerases
  • PDIA3 protein, human