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Deletion of hypoxia‐responsive microRNA‐210 results in a sex‐specific decrease in nephron number
Author(s) -
Hemker Shelby L.,
Cerqueira Débora M.,
Bodnar Andrew J.,
Cargill Kasey R.,
Clugston Andrew,
Anslow Melissa J.,
SimsLucas Sunder,
Kostka Dennis,
Ho Jacqueline
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201902767r
Subject(s) - nephron , kidney development , wnt signaling pathway , kidney , microrna , biology , hypoxia (environmental) , endocrinology , medicine , conditional gene knockout , knockout mouse , kidney disease , microbiology and biotechnology , signal transduction , phenotype , receptor , chemistry , genetics , gene , embryonic stem cell , organic chemistry , oxygen
Low nephron number results in an increased risk of developing hypertension and chronic kidney disease. Intrauterine growth restriction is associated with a nephron deficit in humans, and is commonly caused by placental insufficiency, which results in fetal hypoxia. The underlying mechanisms by which hypoxia impacts kidney development are poorly understood. microRNA‐210 is the most consistently induced microRNA in hypoxia and is known to promote cell survival in a hypoxic environment. In this study, the role of microRNA‐210 in kidney development was evaluated using a global microRNA‐210 knockout mouse. A male‐specific 35% nephron deficit in microRNA‐210 knockout mice was observed. Wnt/β‐catenin signaling, a pathway crucial for nephron differentiation, was misregulated in male kidneys with increased expression of the canonical Wnt target lymphoid enhancer binding factor 1. This coincided with increased expression of caspase‐8‐associated protein 2 , a known microRNA‐210 target and apoptosis signal transducer. Together, these data are consistent with a sex‐specific requirement for microRNA‐210 in kidney development.