Get started
Work

MANF clears mutant uromodulin in human kidney organoids of autosomal dominant tubulointerstitial kidney disease

Year: 2026
Type: article
Abstract: Autosomal dominant tubulointerstitial kidney disease due to uromodulin mutations (ADTKD-UMOD) is one of the leading hereditary kidney diseases. Currently there is no targeted treatment. To illuminate human relevance of mesencephalic astrocyte-derived neurotrophic factor (MANF)-based therapy, we have established patient induced pluripotent stem cell (iPSC)-derived kidney organoid model carrying UMOD p.H177-R185del, the leading mutation causing ADTKD. We have discovered that MANF can directly bind and repress ER calcium release channel IP3R1, thus enhancing AMPK-induced autophagy in a TRIB3-dependent manner. The therapeutic implication of this finding may well be extended to other protein misfolding diseases.
DOI: 10.1172/jci205631
Authors: Chenjian Gu, Yili Fang, Yixuan Wang, Eric Tycksen, Gayathri Kondepati, Chuang Li, Kendrah O. Kidd, Jun Liu, Fumihiko Urano, Maria Lindahl, Anthony J. Bleyer, Srikanth Singamaneni, Zhao Sun, Ying Maggie Chen
Institutions: Washington University in St. Louis, Genome Technology Access Center, Wake Forest University Health Sciences, Wake Forest University, Shanghai First People's Hospital, University of Helsinki, The University of Texas at Dallas, St. Louis VA Medical Center
Language: English
Subfield: Genetics
Open Access status: gold
Estimated APC paid: $5,200
Funders: American Heart Association, American Society of Nephrology, Center for Selective C-H Functionalization, National Science Foundation, Academy of Finland, Diabetestutkimussäätiö, National Center for Research Resources, Congressionally Directed Medical Research Programs
OpenAlex ID: W7133303563
FWCI:
Cites: 3
Cited by:
Related to: