Open AccessSickle cell disease up‐regulates vasopressin, aquaporin 2, urea transporter A1, Na‐K‐Cl cotransporter 2, and epithelial Na channels in the mouse kidney medulla despite compromising urinary concentration ability
Author(s) -
Wang Hong,
Morris Ryan G.,
Knepper Mark A.,
Zhou Xiaoming
Publication year - 2019
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.14066
Subject(s) - vasopressin , aquaporin 2 , endocrinology , medicine , urinary system , cotransporter , kidney , chemistry , apical membrane , biology , sodium , biochemistry , mechanical engineering , water channel , engineering , inlet , membrane , organic chemistry
Sickle cell disease ( SCD )‐induced urinary concentration defect has been proposed as caused by impaired ability of the occluded vasa recta due to red blood cell sickling to serve as countercurrent exchangers and renal tubules to absorb water and solutes. However, the exact molecular mechanisms remain largely unknown. The present studies were undertaken to determine the effects of SCD on vasopressin, aquaporin2 ( AQP 2), urea transporter A1 ( UTA 1), Na‐K‐Cl co‐transporter 2 ( NKCC 2), epithelial Na channels ( EN aC), aquaporin1 ( AQP 1), nuclear factor of activated T cells 5 ( NFAT 5) and Src homology region‐2 domain‐containing phosphatase‐1 ( SHP ‐1), an important regulator of NFAT 5, in the Berkeley SCD mouse kidney medulla. Under water repletion, SCD only induced a minor urinary concentration defect associated with increased urinary vasopressin level alone with the well‐known effects of vasopressin: protein abundance of AQP 2, UTA 1 and EN aC‐ β and apical targeting of AQP 2 as compared with non‐ SCD . SCD did not significantly affect AQP 1 protein level. Water restriction had no further significant effect on SCD urinary vasopressin. NFAT 5 is also critical to urinary concentration. Instead, water restriction‐activated NFAT 5 associated with inhibition of SHP ‐1 in the SCD mice. Yet, water restriction only elevated urinary osmolality by 28% in these mice as opposed to 104% in non‐ SCD mice despite similar degree increases of protein abundance of AQP 2, NKCC 2 and AQP 2‐S256‐P. Water‐restriction had no significant effect on protein abundance of EN aC or AQP 1 in either strain. In conclusion, under water repletion SCD , only induces a minor defect in urinary concentration because of compensation from the up‐regulated vasopressin system. However, under water restriction, SCD mice struggle to concentrate urine despite activating NFAT 5. SCD ‐induced urinary concentration defect appears to be resulted from the poor blood flow in vasa recta rather than the renal tubules’ ability to absorb water and solutes.