Thiazolidinediones Enhance Sodium-Coupled Bicarbonate Absorption from Renal Proximal Tubules via PPARγ-Dependent Nongenomic Signaling

被引：55

作者：

Endo, Yoko ^{[1
]}

Suzuki, Masashi ^{[1
]}

Yamada, Hideomi ^{[1
]}

Horita, Shoko ^{[1
]}

Kunimi, Motoei ^{[1
]}

Yamazaki, Osamu ^{[1
]}

Shirai, Ayumi ^{[1
]}

Nakamura, Motonobu ^{[1
]}

Iso-O, Naoyuki ^{[1
]}

Li, Yuehong ^{[1
,3
]}

Hara, Masumi ^{[1
]}

Tsukamoto, Kazuhisa ^{[1
]}

Moriyama, Nobuo ^{[4
]}

Kudo, Akihiko ^{[5
]}

Kawakami, Hayato ^{[5
]}

Yamauchi, Toshimasa ^{[1
]}

Kubota, Naoto ^{[1
]}

Kadowaki, Takashi ^{[1
]}

Kume, Haruki ^{[2
]}

Enomoto, Yutaka ^{[2
]}

Homma, Yukio ^{[2
]}

Seki, George ^{[1
]}

Fujita, Toshiro ^{[1
]}

机构：

[1] Univ Tokyo, Dept Internal Med, Tokyo 1130033, Japan

[2] Univ Tokyo, Dept Urol, Fac Med, Tokyo 1130033, Japan

[3] Peking Univ, Dept Nephrol, Peoples Hosp, Beijing 100044, Peoples R China

[4] Fukuoka Prefectural Univ, Dept Expt Nursing, Fac Nursing, Fukuoka 8258585, Japan

[5] Kyorin Univ, Dept Anat, Sch Med, Tokyo 1818611, Japan

来源：

CELL METABOLISM | 2011年 / 13卷 / 05期

关键词：

INDUCED FLUID RETENTION; GROWTH-FACTOR-RECEPTOR; BIPHASIC REGULATION; CELLULAR ACIDOSIS; UP-REGULATION; CELLS; TRANSPORT; STIMULATION; ACTIVATION; ESTROGEN;

D O I：

10.1016/j.cmet.2011.02.015

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Thiazolidinediones (TZDs) improve insulin resistance by activating a nuclear hormone receptor, peroxisome proliferator-activated receptor gamma (PPAR gamma). However, the use of TZDs is associated with plasma volume expansion through a mechanism that remains to be clarified. Here we showed that TZDs rapidly stimulate sodium-coupled bicarbonate absorption from the renal proximal tubule in vitro and in vivo. TZD-induced transport stimulation is dependent on PPAR gamma-Src-EGFR-ERK and observed in rat, rabbit and human, but not in mouse proximal tubules where Src-EGFR is constitutively activated. The existence of PPAR gamma-Src-dependent nongenomic signaling, which requires the ligand-binding ability, but not the transcriptional activity of PPAR gamma, is confirmed in mouse embryonic fibroblast cells. The enhancement of the association between PPAR gamma and Src by TZDs supports an indispensable role of Src in this signaling. These results suggest that the PPAR gamma-dependent nongenomic stimulation of renal proximal transport is also involved in TZD-induced volume expansion.

引用

页码：550 / 561

页数：12

共 42 条

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Peroxisome proliferator-activated receptor-γ upregulates caveolin-1 and caveolin-2 expression in human carcinoma cells [J].