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MANF clears mutant uromodulin in human kidney organoids of autosomal dominant tubulointerstitial kidney disease
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
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
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Research Letter Genetics Nephrology

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

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Abstract

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

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Figure 1

MANF promotes UMOD proteostasis by regulating IP3R1-mediated ER calcium efflux in ADTKD kidney organoids.

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MANF promotes UMOD proteostasis by regulating IP3R1-mediated ER calcium ...
(A) WB of UMOD in organoids. (B) Bright-field or double-IF of UMOD and BiP with DAPI in organoids. (C, F, and I) IB of indicated proteins in organoid-isolated TALs. (D) Luciferase activity in the organoid medium. (E) Transcript expression of ER calcium efflux channels in organoid-derived TALs. (G) IF of IP3R1 and UMOD. (H) Dual-IF staining of TRIB3 and UMOD. (J) Co-IP demonstrating the association of TRIB3 and AMPKα in TALs. (K–R) Organoids were treated without or with DOX from days 22–30. (K and N–P) IB of the indicated proteins in TALs. (L) Co-IP showing the interaction between MANF and IP3R1 in TALs with DOX. (M) Luciferase activity in the organoid medium. (Q) p-FLISA of cytokines in the organoid medium. (R) Heatmap of TAL healthy state markers. Benjamini-Hochberg adjusted P < 0.05. *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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