Deletion of the Mammalian Homolog of Yeast Vacuolar Protein Sorting 34 Inhibits Compensatory Nephron Hypertrophy

Hdl Handle:
http://hdl.handle.net/10675.2/600893
Title:
Deletion of the Mammalian Homolog of Yeast Vacuolar Protein Sorting 34 Inhibits Compensatory Nephron Hypertrophy
Authors:
Liu, Ting
Abstract:
Reduction of functioning nephrons stimulates all components of the remaining nephrons, particularly the proximal tubule, to undergo compensatory nephron hypertrophy (CNH). Recent studies in our lab revealed activation of the mammalian homolog of yeast vacuolar protein sorting 34 (mVPS34) in the remaining kidney within 30 min in response to uninephrectomy (UNX). Interestingly, mVPS34 has been reported to be an upstream mediator of mTORC1 activation in cultured cells. However, whether mVPS34 activation is essential in mediating mTORC1 signaling to CNH in vivo remains unknown. We crossed mVPS34flox/flox mice with SG.Cre mice expressing tamoxifen-inducible Cre recombinase mainly in the S1 and S2 segments of the proximal tubule and generated proximal tubule-specific mVPS34 knockout (mVPS34ptKO) mice. The body weight and kidney/body weight ratio (K/Bwt) of mVPS34ptKO mice were similar to those of wild type control (mVPS34Ctrl) littermates. 8-week-old mVPS34Ctrl and mVPS34ptKO mice were uninephrectomized. UNX-induced CNH in mVPS34ptKO mice was blocked by 40-55%, as indicated by inhibition of increases in K/Bwt ratio compared to that of mVPS34Ctrl mice (15.81±2.82 vs. 33.15±1.97%; p<0.001, n=7-9). There was no change in BUN levels in mVPS34ptKO and mVPS34ctrl mice with or without UNX. This study provided the first genetic evidence that mVPS34 mediates 40-55% of CNH. Further studies will determine the interactions between mVPS34 activation and mTORC1 signaling in regulating CNH.
Affiliation:
Department of Cellular Biology and Anatomy
Issue Date:
Mar-2016
URI:
http://hdl.handle.net/10675.2/600893
Type:
Other
Language:
en_US
Description:
Poster presented at the 2016 Graduate Research Day
Appears in Collections:
2016 Graduate Research Day; Department of Cellular Biology and Anatomy: Student Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorLiu, Tingen
dc.date.accessioned2016-03-08T13:36:07Zen
dc.date.available2016-03-08T13:36:07Zen
dc.date.issued2016-03en
dc.identifier.urihttp://hdl.handle.net/10675.2/600893en
dc.descriptionPoster presented at the 2016 Graduate Research Dayen
dc.description.abstractReduction of functioning nephrons stimulates all components of the remaining nephrons, particularly the proximal tubule, to undergo compensatory nephron hypertrophy (CNH). Recent studies in our lab revealed activation of the mammalian homolog of yeast vacuolar protein sorting 34 (mVPS34) in the remaining kidney within 30 min in response to uninephrectomy (UNX). Interestingly, mVPS34 has been reported to be an upstream mediator of mTORC1 activation in cultured cells. However, whether mVPS34 activation is essential in mediating mTORC1 signaling to CNH in vivo remains unknown. We crossed mVPS34flox/flox mice with SG.Cre mice expressing tamoxifen-inducible Cre recombinase mainly in the S1 and S2 segments of the proximal tubule and generated proximal tubule-specific mVPS34 knockout (mVPS34ptKO) mice. The body weight and kidney/body weight ratio (K/Bwt) of mVPS34ptKO mice were similar to those of wild type control (mVPS34Ctrl) littermates. 8-week-old mVPS34Ctrl and mVPS34ptKO mice were uninephrectomized. UNX-induced CNH in mVPS34ptKO mice was blocked by 40-55%, as indicated by inhibition of increases in K/Bwt ratio compared to that of mVPS34Ctrl mice (15.81±2.82 vs. 33.15±1.97%; p<0.001, n=7-9). There was no change in BUN levels in mVPS34ptKO and mVPS34ctrl mice with or without UNX. This study provided the first genetic evidence that mVPS34 mediates 40-55% of CNH. Further studies will determine the interactions between mVPS34 activation and mTORC1 signaling in regulating CNH.en
dc.language.isoen_USen
dc.subjectNephronsen
dc.subjectMiceen
dc.subjectHypertrophyen
dc.titleDeletion of the Mammalian Homolog of Yeast Vacuolar Protein Sorting 34 Inhibits Compensatory Nephron Hypertrophyen_US
dc.typeOtheren
dc.contributor.departmentDepartment of Cellular Biology and Anatomyen
dc.description.advisorChen, Jian-Kangen
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