Transcription factors AP-2α and AP-2β regulate distinct segments of the distal nephron in the mammalian kidney.
Transcription factors AP-2α and AP-2β regulate distinct segments of the distal nephron in the mammalian kidney.
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DOI：
10.1038/s41467-022-29644-3
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发表时间：
2022-04-25
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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转录因子AP-2α和AP-2β被认为调节肾单位前体群体向远端肾单位节段的分化。在这里，我们发现在成年哺乳动物肾脏中，AP-2α存在于髓质集合管中，而AP-2β存在于除髓质集合管之外的远端肾单位段中。肾单位祖细胞中AP-2α的失活不影响哺乳动物的肾发生，而其在集合管中的失活导致成人髓质集合管的缺陷。肾单位祖细胞中AP-2β的杂合性导致进行性远曲小管异常和β-catenin/mTOR过度活化，这与肾纤维化和囊肿相关。肾单位祖细胞中AP-2β的完全缺失导致远曲小管缺失、肾囊肿和纤维化伴β-连环蛋白/mTOR过度活化以及出生后早期死亡。因此，AP-2α和AP-2β在哺乳动物肾脏远端肾单位的不同节段中具有非冗余的不同时空功能。远端肾单位在肾脏发育过程中是如何形成的一直很难研究。在这里，他们表明AP-2β是远曲小管的形成和出生后功能所必需的，而AP-2α在维持髓集合管的结构中起作用。
Transcription factors AP-2α and AP-2β have been suggested to regulate the differentiation of nephron precursor populations towards distal nephron segments. Here, we show that in the adult mammalian kidney AP-2α is found in medullary collecting ducts, whereas AP-2β is found in distal nephron segments except for medullary collecting ducts. Inactivation of AP-2α in nephron progenitor cells does not affect mammalian nephrogenesis, whereas its inactivation in collecting ducts leads to defects in medullary collecting ducts in the adult. Heterozygosity for AP-2β in nephron progenitor cells leads to progressive distal convoluted tubule abnormalities and β-catenin/mTOR hyperactivation that is associated with renal fibrosis and cysts. Complete loss of AP-2β in nephron progenitor cells caused an absence of distal convoluted tubules, renal cysts, and fibrosis with β-catenin/mTOR hyperactivation, and early postnatal death. Thus, AP-2α and AP-2β have non-redundant distinct spatiotemporal functions in separate segments of the distal nephron in the mammalian kidney. How the distal nephron is patterned during kidney development has been difficult to study. Here they show that AP-2β is required for the formation and postnatal function of distal convoluted tubules, whereas AP-2α has a role in maintaining the structure of medullary collecting ducts.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
7.7
作者：
Lindström NO;Lawrence ML;Burn SF;Johansson JA;Bakker ER;Ridgway RA;Chang CH;Karolak MJ;Oxburgh L;Headon DJ;Sansom OJ;Smits R;Davies JA;Hohenstein P
通讯作者：
Hohenstein P
影响因子：
4.6
作者：
Chambers, Brooke E.;Gerlach, Gary F.;Wingert, Rebecca A.
通讯作者：
Wingert, Rebecca A.
影响因子：
4.6
作者：
Knight, RD;Javidan, Y;Schilling, TF
通讯作者：
Schilling, TF
影响因子：
11.8
作者：
Marneros, Alexander G.
通讯作者：
Marneros, Alexander G.