Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction
Summary: Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004223004157 |
| _version_ | 1797867606550511616 |
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| author | Huanjuan Su Zhichen Yang Ying Zhang Bihui Yang Zhanmei Zhou Cailing Su Wei Cao |
| author_facet | Huanjuan Su Zhichen Yang Ying Zhang Bihui Yang Zhanmei Zhou Cailing Su Wei Cao |
| author_sort | Huanjuan Su |
| collection | DOAJ |
| description | Summary: Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of virus tracing and optogenetic techniques to identify an overactive central pathway in the paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) that determines the fibrotic fate of kidney after relief of the obstruction. The overactive pathway is driven by kidney afferent nerves that activate angiotensin II signaling in RVLM-projecting PVN neurons to drive sympathetic discharge back to the kidney. This causes the kidney to undergo fibrosis with loss of function. Blockade of sympathetic traffic or deletion of AT1a in PVN preserves the structure of the post-obstructed kidney. Human post-obstructed kidneys also demonstrate evidence of increased sympathetic nerve activity associated with a fibrotic outcome. Manipulating these neural elements is a potential treatment strategy. |
| first_indexed | 2024-04-09T23:42:50Z |
| format | Article |
| id | doaj.art-8c814bf32f144c4ea219d2fb4430cd02 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-09T23:42:50Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-8c814bf32f144c4ea219d2fb4430cd022023-03-18T04:42:33ZengElsevieriScience2589-00422023-04-01264106338Neural and central mechanisms of kidney fibrosis after relief of ureteral obstructionHuanjuan Su0Zhichen Yang1Ying Zhang2Bihui Yang3Zhanmei Zhou4Cailing Su5Wei Cao6Division of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. ChinaDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. China; Division of Nephrology, The Third Affiliated Hospital of Southern Medical University, 183 West Zhongshan Avenue, Guangzhou 510630, P. R. ChinaDivision of Nephrology, The Second Affiliated Hospital of Guangzhou Medical University, Changgang East Road, Guangzhou 510260, P. R. ChinaDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. ChinaDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. ChinaDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. ChinaDivision of Nephrology, Nanfang Hospital, Southern Medical University, State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Nephrology, 1838 North Guangzhou Avenue, Guangzhou 510515, P. R. China; Corresponding authorSummary: Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of virus tracing and optogenetic techniques to identify an overactive central pathway in the paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) that determines the fibrotic fate of kidney after relief of the obstruction. The overactive pathway is driven by kidney afferent nerves that activate angiotensin II signaling in RVLM-projecting PVN neurons to drive sympathetic discharge back to the kidney. This causes the kidney to undergo fibrosis with loss of function. Blockade of sympathetic traffic or deletion of AT1a in PVN preserves the structure of the post-obstructed kidney. Human post-obstructed kidneys also demonstrate evidence of increased sympathetic nerve activity associated with a fibrotic outcome. Manipulating these neural elements is a potential treatment strategy.http://www.sciencedirect.com/science/article/pii/S2589004223004157Biological sciencesNeuroscienceSystems neuroscience |
| spellingShingle | Huanjuan Su Zhichen Yang Ying Zhang Bihui Yang Zhanmei Zhou Cailing Su Wei Cao Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction iScience Biological sciences Neuroscience Systems neuroscience |
| title | Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| title_full | Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| title_fullStr | Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| title_full_unstemmed | Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| title_short | Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| title_sort | neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction |
| topic | Biological sciences Neuroscience Systems neuroscience |
| url | http://www.sciencedirect.com/science/article/pii/S2589004223004157 |
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