TY - JOUR
T1 - Endoplasmic reticulum-associated biomarkers for molecular phenotyping of rare kidney disease
AU - Li, Chuang
AU - Chen, Ying Maggie
N1 - Funding Information:
Funding: Y.M.C. is supported by NIH grants R01 DK105056, R03DK106451 and K08DK089015, the Office of the Assistant Secretary of Defense for Health Affairs through the Peer Reviewed Medical Research Program under Award W81XWH-19-1-0320, George M. O’Brien Kidney Research Core Center (NU GoKidney, NIH P30 DK114857), Mallinckrodt Challenge Grant, and Washington University Center for Drug Discovery, Investigator Matching Micro Grant.
Funding Information:
Acknowledgments: Y.M.C. is a member of Washington University Diabetes Research Center (supported by NIH P30 DK020579), Washington University Musculoskeletal Research Center (supported by NIH P30AR057235), and Washington University Institute of Clinical and Translational Sciences (UL1 TR000448).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/2/2
Y1 - 2021/2/2
N2 - The endoplasmic reticulum (ER) is the central site for folding, post-translational modifi-cations, and transport of secretory and membrane proteins. An imbalance between the load of mis-folded proteins and the folding capacity of the ER causes ER stress and an unfolded protein re-sponse. 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.
AB - The endoplasmic reticulum (ER) is the central site for folding, post-translational modifi-cations, and transport of secretory and membrane proteins. An imbalance between the load of mis-folded proteins and the folding capacity of the ER causes ER stress and an unfolded protein re-sponse. 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.
KW - Biomarkers
KW - Endoplasmic reticulum
KW - Kidney disease
UR - http://www.scopus.com/inward/record.url?scp=85101183547&partnerID=8YFLogxK
U2 - 10.3390/ijms22042161
DO - 10.3390/ijms22042161
M3 - Review article
C2 - 33671535
AN - SCOPUS:85101183547
SN - 1661-6596
VL - 22
SP - 1
EP - 13
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 4
M1 - 2161
ER -