SETD2 regulates SLC family transporter-mediated sodium and glucose reabsorptions in renal tubule

Taku Mitome, Hiromichi Wakui, Kengo Azushima, Tatsuki Uehara, Ryosuke Jikuya, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Hiroki Ito, Takashi Kawahara, Mitsuru Komeya, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Kiyotaka NagahamaAkira Nishiyama, Tomohiko Tamura, Yayoi Kimura, Tatsukata Kawagoe, Nobuhisa Mizuki, Gang Huang, Hiroji Uemura, Masahiro Yao, Kazuhide Makiyama, Kouichi Tamura, Hisashi Hasumi

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number150730
JournalBiochemical and Biophysical Research Communications
Volume734
DOIs
StatePublished - Nov 19 2024
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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