Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel.
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....
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0223496 |
| _version_ | 1819123703486611456 |
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| author | Keiichiro Mishima Masao Nakasatomi Shunsuke Takahashi Hidekazu Ikeuchi Toru Sakairi Yoriaki Kaneko Keiju Hiromura Yoshihisa Nojima Akito Maeshima |
| author_facet | Keiichiro Mishima Masao Nakasatomi Shunsuke Takahashi Hidekazu Ikeuchi Toru Sakairi Yoriaki Kaneko Keiju Hiromura Yoshihisa Nojima Akito Maeshima |
| author_sort | Keiichiro Mishima |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T07:12:34Z |
| format | Article |
| id | doaj.art-1c598242fc214e368f3ef4813e3103f6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T07:12:34Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-1c598242fc214e368f3ef4813e3103f62022-12-21T18:34:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-011410e022349610.1371/journal.pone.0223496Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel.Keiichiro MishimaMasao NakasatomiShunsuke TakahashiHidekazu IkeuchiToru SakairiYoriaki KanekoKeiju HiromuraYoshihisa NojimaAkito MaeshimaThe 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.https://doi.org/10.1371/journal.pone.0223496 |
| spellingShingle | Keiichiro Mishima Masao Nakasatomi Shunsuke Takahashi Hidekazu Ikeuchi Toru Sakairi Yoriaki Kaneko Keiju Hiromura Yoshihisa Nojima Akito Maeshima Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. PLoS ONE |
| title | Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. |
| title_full | Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. |
| title_fullStr | Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. |
| title_full_unstemmed | Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. |
| title_short | Attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the N-type calcium channel. |
| title_sort | attenuation of renal fibrosis after unilateral ureteral obstruction in mice lacking the n type calcium channel |
| url | https://doi.org/10.1371/journal.pone.0223496 |
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