The role of PPARγ in kidney collecting-duct

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Publication Type dissertation
School or College School of Medicine
Department Physiology
Author Zhang, Hui
Title The role of PPARγ in kidney collecting-duct
Date 2011-08
Description The peroxisome proliferator-activated receptor subtype γ (PPARγ) ligands, namely the synthetic insulin-sensitizing thiazolidinedione (TZD) compounds, have demonstrated great potential in the treatment of type II diabetes. However, their clinical applicability is limited by a common and serious side effect of edema. To address the mechanism of TZD-induced edema, we generated mice with collecting duct (CD)-specific disruption of the PPARγ gene. We found that mice with CD knockout of this receptor were resistant to the rosiglitazone- (RGZ) induced increases in body weight and plasma volume expansion found in control mice expressing PPARγ in the CD. RGZ reduced urinary sodium excretion in control and not in conditional knockout mice. Furthermore, RGZ stimulated sodium transport in primary cultures of CD cells expressing PPARγ and not in cells lacking this receptor. These findings demonstrate a PPARγ-dependent pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention. To further study the mechanism of increased fluid reabsorption in the distal nephron in response to PPARγ agonist, we performed electrophysiological studies on primary IMCD cells to investigate the involvement of ENaC in mediating TZD-induced fluid reabsorption. RGZ treatment timedependently inhibited the activity and expression of ENaC, the major route of transcellular transport in the CD. However, RGZ treatment decreased the iv transepithelial resistance. Since ENaC was suppressed, the reduction of the TER indicated that there is an alternative pathway in regulation of sodium transport in the CD that underlies TZD-induced fluid retention.
Type Text
Publisher University of Utah
Subject MESH PPAR gamma; Kidney Tubules, Collecting; Diabetes Mellitus, Type 2; Insulin; Thiazolidinediones; Zinc Fingers; Urinary Retention; Hyperlipidemias; Receptors, Cytoplasmic and Nuclear; Transcription Factors; Signal Transduction
Dissertation Institution University of Utah
Dissertation Name Doctor of Philosophy
Language eng
Relation is Version of Digital reproduction of The Role of PPARγ in Kidney Collecting-Duct. Spencer S. Eccles Health Sciences Library. Print version available at J. Willard Marriott Library Special Collections.
Rights Management Copyright © Hui Zhang 2011
Format Medium application/pdf
Format Extent 8,309,130 bytes
Source Original in Marriott Library Special Collections,
ARK ark:/87278/s6rz2m97
Setname ir_etd
Date Created 2014-05-20
Date Modified 2021-12-13
ID 196431
Reference URL https://collections.lib.utah.edu/ark:/87278/s6rz2m97
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