The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation
The Na+/H+ exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation
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DOI：
10.1152/ajpgi.00332.2003
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发表时间：
2004-07-01
影响因子：
4.5
通讯作者：
Seidler, U
中科院分区：
文献类型：
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作者：
Bachmann, O;Riederer, B;Seidler, U
Na+/H+交换器亚型NHE 2在肠道中高度表达，但其生理作用仍不清楚。本研究的目的是确定其在小鼠结肠中的表达、定位和调节特性，并寻找NHE 2（-/-）结肠中允许正常组织学和吸收功能的代偿性变化。为此，我们测量了小鼠近端结肠表面和隐窝细胞NHE 1，NHE 2和NHE 3表达水平，小鼠近端结肠隐窝中对酸，高渗透压和cAMP的转运率，以及NHE 2（-/-）隐窝中转录水平和酸激活的NHE活性的变化。我们发现，NHE 2在隐窝中表达最丰富，NHE 1在隐窝和表面细胞中表达相同，NHE 3在表面细胞中表达更强。与NHE 1一样，NHE 2被低细胞内pH（pH（i））、高渗透压和cAMP激活，而NHE 3仅被低pH激活。从NHE 2（-/-）小鼠分离的隐窝显示增加的酸活化NHE 1-和NHE 3-归因于Na+/H+交换活性，NHE 1表达无变化，NHE 3表达水平是正常同窝出生小鼠的两倍。NHE 2（-/-）结肠细胞超微结构无明显变化。我们的研究结果表明NHE 2在隐窝中的高表达，并表明NHE 2在隐窝pH（i）和体积稳态中的作用。
The Na+/H+ exchanger isoform NHE2 is highly expressed in the intestinal tract, but its physiological role has remained obscure. The aim of this study was to define its expression, location, and regulatory properties in murine colon and to look for the compensatory changes in NHE2 ( -/-) colon that allow normal histology and absorptive function. To this end, we measured murine proximal colonic surface and crypt cell NHE1, NHE2, and NHE3 expression levels, transport rates in response to acid, hyperosmolarity and cAMP in murine proximal colonic crypts, as well as changes in transcript levels and acid-activated NHE activity in NHE2 (-/-) crypts. We found that NHE2 was expressed most abundantly in crypts, NHE1 equally in crypts and surface cells, and NHE3 much stronger in surface cells. NHE2, like NHE1, was activated by low intracellular pH (pH(i)), hyperosmolarity, and cAMP, whereas NHE3 was activated only by low pHi. Crypts isolated from NHE2 (-/-) mice displayed increased acid-activated NHE1- and NHE3-attributable Na+/H+ exchange activity, no change in NHE1 expression, and NHE3 expression levels twice as high as in normal littermates. No change in cellular ultrastructure was found in NHE2 (-/-) colon. Our results demonstrate high NHE2 expression in the crypts and suggest a role for NHE2 in cryptal pH(i) and volume homeostasis.