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- W2911596411 abstract "SEC63 encodes a resident protein in the endoplasmic reticulum membrane that, when mutated, causes human autosomal dominant polycystic liver disease. Selective inactivation of Sec63 in all distal nephron segments in embryonic mouse kidney results in polycystin-1-mediated polycystic kidney disease (PKD). It also activates the Ire1α-Xbp1 branch of the unfolded protein response, producing Xbp1s, the active transcription factor promoting expression of specific genes to alleviate endoplasmic reticulum stress. Simultaneous inactivation of Xbp1 and Sec63 worsens PKD in this model.We explored the renal effects of postnatal inactivation of Sec63 alone or with concomitant inactivation of Xbp1 or Ire1α, specifically in the collecting ducts of neonatal mice.The later onset of inactivation of Sec63 restricted to the collecting duct does not result in overt activation of the Ire1α-Xbp1 pathway or cause polycystin-1-dependent PKD. Inactivating Sec63 along with either Xbp1 or Ire1α in this model causes interstitial inflammation and associated fibrosis with decline in kidney function over several months. Re-expression of XBP1s in vivo completely rescues the chronic kidney injury observed after inactivation of Sec63 with either Xbp1 or Ire1α.In the absence of Sec63, basal levels of Xbp1s activity in collecting ducts is both necessary and sufficient to maintain proteostasis (protein homeostasis) and protect against inflammation, myofibroblast activation, and kidney functional decline. The Sec63-Xbp1 double knockout mouse offers a novel genetic model of chronic tubulointerstitial kidney injury, using collecting duct proteostasis defects as a platform for discovery of signals that may underlie CKD of disparate etiologies." @default.
- W2911596411 created "2019-02-21" @default.
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- W2911596411 date "2019-02-11" @default.
- W2911596411 modified "2023-10-14" @default.
- W2911596411 title "Spliced XBP1 Rescues Renal Interstitial Inflammation Due to Loss of Sec63 in Collecting Ducts" @default.
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- W2911596411 cites W1215049722 @default.
- W2911596411 cites W1543695514 @default.
- W2911596411 cites W1546139069 @default.
- W2911596411 cites W1550903142 @default.
- W2911596411 cites W1827490702 @default.
- W2911596411 cites W1922472632 @default.
- W2911596411 cites W1947959231 @default.
- W2911596411 cites W1963767630 @default.
- W2911596411 cites W1965071252 @default.
- W2911596411 cites W1967883750 @default.
- W2911596411 cites W1977410954 @default.
- W2911596411 cites W1981137206 @default.
- W2911596411 cites W1987680142 @default.
- W2911596411 cites W1998357223 @default.
- W2911596411 cites W1998466702 @default.
- W2911596411 cites W1999870654 @default.
- W2911596411 cites W2003755766 @default.
- W2911596411 cites W2005039062 @default.
- W2911596411 cites W2011924388 @default.
- W2911596411 cites W2017841719 @default.
- W2911596411 cites W2031515819 @default.
- W2911596411 cites W2031735388 @default.
- W2911596411 cites W2034126562 @default.
- W2911596411 cites W2036677133 @default.
- W2911596411 cites W2038725731 @default.
- W2911596411 cites W2039775393 @default.
- W2911596411 cites W2042641050 @default.
- W2911596411 cites W2048086508 @default.
- W2911596411 cites W2053500970 @default.
- W2911596411 cites W2054897365 @default.
- W2911596411 cites W2062141110 @default.
- W2911596411 cites W2063972197 @default.
- W2911596411 cites W2068568471 @default.
- W2911596411 cites W2071767704 @default.
- W2911596411 cites W2078277615 @default.
- W2911596411 cites W2100526574 @default.
- W2911596411 cites W2104010513 @default.
- W2911596411 cites W2107211482 @default.
- W2911596411 cites W2107504852 @default.
- W2911596411 cites W2108455760 @default.
- W2911596411 cites W2109922521 @default.
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- W2911596411 cites W2120815988 @default.
- W2911596411 cites W2122084492 @default.
- W2911596411 cites W2122345674 @default.
- W2911596411 cites W2124686901 @default.
- W2911596411 cites W2127639686 @default.
- W2911596411 cites W2127906377 @default.
- W2911596411 cites W2138561620 @default.
- W2911596411 cites W2140406255 @default.
- W2911596411 cites W2143952529 @default.
- W2911596411 cites W2144465887 @default.
- W2911596411 cites W2147810846 @default.
- W2911596411 cites W2148407960 @default.
- W2911596411 cites W2149766325 @default.
- W2911596411 cites W2157515789 @default.
- W2911596411 cites W2164032619 @default.
- W2911596411 cites W2167055272 @default.
- W2911596411 cites W2252909698 @default.
- W2911596411 cites W2317177510 @default.
- W2911596411 cites W2415942083 @default.
- W2911596411 cites W2471427314 @default.
- W2911596411 cites W2607216118 @default.
- W2911596411 cites W2744015406 @default.
- W2911596411 cites W2764162783 @default.
- W2911596411 cites W2775230765 @default.
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- W2911596411 doi "https://doi.org/10.1681/asn.2018060614" @default.
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- W2911596411 hasPublicationYear "2019" @default.
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