Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel


Autoři: Keiichiro Mishima aff001;  Masao Nakasatomi aff001;  Shunsuke Takahashi aff001;  Hidekazu Ikeuchi aff001;  Toru Sakairi aff001;  Yoriaki Kaneko aff001;  Keiju Hiromura aff001;  Yoshihisa Nojima aff001;  Akito Maeshima aff001
Působiště autorů: Department of Nephrology and Rheumatology, Gunma University Graduate School of Medicine, Maebashi, Japan aff001
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0223496

Souhrn

The N-type Ca2+ channel (Cav2.2) is distributed in sympathetic nerves that innervate the tubules, the vessels, and the juxtaglomerular granular cells of the kidney. However, the role of N-type Ca2+ channels in renal disease remains unknown. To address this issue, Cav2.2 knockout mice were utilized. Immunoreactive Cav2.2 was undetectable in normal kidneys of C57BL/6N mice, but it became positive in the interstitial S100-positive nerve fibers after unilateral ureteral obstruction (UUO). There were no significant differences in mean blood pressure, heart rate, and renal function between wild-type littermates and Cav2.2-knockout mice at baseline, as well as after UUO. Cav2.2 deficiency significantly reduced the EVG-positive fibrotic area, alpha-SMA expression, the production of type I collagen, and the hypoxic area in the obstructed kidneys. The expression of tyrosine hydroxylase, a marker for sympathetic neurons, was significantly increased in the obstructed kidneys of wild-type mice, but not in Cav2.2-knockout mice. These data suggest that increased Cav2.2 is implicated in renal nerve activation leading to the progression of renal fibrosis. Blockade of Cav2.2 might be a novel therapeutic approach for preventing renal fibrosis.

Klíčová slova:

Fibrosis – Hypoxia – Immunostaining – Kidneys – Mouse models – Nerve fibers – Quantitative analysis – Renal system


Zdroje

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