Physiological oxygenation status is required for fully differentiated phenotype in kidney cortex proximal tubules

被引:14
作者
de Laplanche, Elodie
Gouget, Karine
Cleris, Guilhem
Dragounoff, Franck
Demont, Jocelyne
Morales, Anne
Bezin, Laurent
Godinot, Catherine
Perriere, Guy
Mouchiroud, Dominique
Simonnet, Helene
机构
[1] Univ Lyon 1, CNRS, UMR 5534, Ctr Genet Mol & Cellulaire, F-69622 Villeurbanne, France
[2] Univ Lyon 1, Unit 5558, Lab Biometrie & Biol Evaluat, F-69622 Villeurbanne, France
[3] Univ Lyon 1, Lab Physiol Integrat Cellulaire & Mol, Unit 5123, F-69622 Villeurbanne, France
[4] Univ Lyon 1, F-69622 Villeurbanne, France
关键词
gene expression profiling; hypoxia; cell adhesion; metabolism; aging;
D O I
10.1152/ajprenal.00022.2006
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
Hypoxia has been suspected to trigger transdifferentiation of renal tubular cells into myofibroblasts in an epithelial-to-mesenchymal transition (EMT) process. To determine the functional networks potentially altered by hypoxia, rat renal tubule suspensions were incubated under three conditions of oxygenation ranging from normoxia (lactate uptake) to severe hypoxia (lactate production). Transcriptome changes after 4 h were analyzed on a high scale by restriction fragment differential display. Among 1,533 transcripts found, 42% were maximally expressed under severe hypoxia and 8% under mild hypoxia (P-O2 = 48 mmHg), suggesting two different levels of oxygen sensing. Normoxia was required for full expression of the proximal tubule-specific transcripts 25-hydroxyvitamin D 1-hydroxylase (Cyp27b1) and L-pyruvate kinase (Pklr), transcripts involved in tissue cohesion such as fibronectin (Fn1) and N-cadherin (Cdh2), and non-muscle-type myosin transcripts. Mild hypoxia increased myogenin transcript level. Conversely, severe hypoxia increased transcripts involved in extracellular matrix remodeling, those of muscle-type myosins, and others involved in creatine phosphate synthesis and lactate transport (Slc16a7). Accordingly, microscopy showed loss of tubule aggregation under hypoxia, without tubular disruption. Hypoxia also increased the levels of kidney-specific transcripts normally restricted to the less oxygenated medullary zone and others specific for the distal part of the nephron. We conclude that extensive oxygen supply to the kidney tubule favors expression of its differentiated functions specifically in the proximal tubule, whose embryonic origin is mesenchymal. The phenotype changes could potentially permit transient adaptation to hypoxia but also favor pathological processes such as tissue invasion.
引用
收藏
页码:F750 / F760
页数:11
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