TY - JOUR
T1 - SETD2 regulates SLC family transporter-mediated sodium and glucose reabsorptions in renal tubule
AU - Mitome, Taku
AU - Wakui, Hiromichi
AU - Azushima, Kengo
AU - Uehara, Tatsuki
AU - Jikuya, Ryosuke
AU - Ohtake, Shinji
AU - Noguchi, Go
AU - Kawaura, Sachi
AU - Iribe, Yasuhiro
AU - Aomori, Kota
AU - Tatenuma, Tomoyuki
AU - Ito, Hiroki
AU - Kawahara, Takashi
AU - Komeya, Mitsuru
AU - Ito, Yusuke
AU - Muraoka, Kentaro
AU - Furuya, Mitsuko
AU - Kato, Ikuma
AU - Fujii, Satoshi
AU - Nagahama, Kiyotaka
AU - Nishiyama, Akira
AU - Tamura, Tomohiko
AU - Kimura, Yayoi
AU - Kawagoe, Tatsukata
AU - Mizuki, Nobuhisa
AU - Huang, Gang
AU - Uemura, Hiroji
AU - Yao, Masahiro
AU - Makiyama, Kazuhide
AU - Tamura, Kouichi
AU - Hasumi, Hisashi
N1 - Publisher Copyright:
© 2024 Elsevier Inc.
PY - 2024/11/19
Y1 - 2024/11/19
N2 - A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.
AB - A regulatory mechanism for SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule, is incompletely understood. Here, we report an important regulation of SLC family transporter by SETD2, a chromatin remodeling gene whose alterations have been found in a subset of kidney cancers. Kidney-specific inactivation of Setd2 resulted in hypovolemia with excessive urine excretion in mouse and interestingly, RNA-sequencing analysis of Setd2-deficient murine kidney exhibited decreased expressions of SLC family transporters, critical transporters for sodium and glucose reabsorptions in renal tubule. Importantly, inactivation of Setd2 in murine kidney displayed attenuated dapagliflozin-induced diuresis and glucose excretion, further supporting that SETD2 might regulate SLCfamily transporter-mediated sodium and glucose reabsorptions in renal tubule. These data uncover an important regulation of SLC family transporter by SETD2, which may illuminate a crosstalk between metabolism and epigenome in renal tubule.
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U2 - 10.1016/j.bbrc.2024.150730
DO - 10.1016/j.bbrc.2024.150730
M3 - Article
C2 - 39366177
AN - SCOPUS:85205369697
SN - 0006-291X
VL - 734
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
M1 - 150730
ER -