Evidence map›Paper›PMID 42892631›Full record

ArticleInflammation research : official journal of the European Histamine Research Society ... [et al.]2026

Imbalance of renin-angiotensin system in calcium oxalate crystals-induced renal oxidative stress and autophagy.

Sen-Yuan Hong, Lin-Tao Miao, Shao-Gang Wang, Yuan-Yuan Yang, Bao-Long Qin

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Article in Inflammation research : official journal of the European Histamine Research Society ... [et al.], 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Sen-Yuan HongDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.ORCID http://orcid.org/0000-0002-0466-0917
Lin-Tao MiaoDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.
Shao-Gang WangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China.
Yuan-Yuan YangDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China. TJyangyuanyuan@163.com.
Bao-Long QinDepartment of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Avenue, Wuhan, 430030, China. 771747457@qq.com.

Funding

National Natural Science Foundation of China 81900646National Natural Science Foundation of China 82500933
6 · The paper itself

Abstract

backgroundCalcium oxalate (CaOx) stones are the most prevalent urological calculi with high incidence and recurrence. Effective preventive drugs remain lacking because of unclear pathogenesis. Although the imbalance of the dual renin-angiotensin system (RAS) axes is closely linked to oxidative stress and autophagy, its role in CaOx stone formation remains undefined.

methodsIn vitro, human renal tubular epithelial cells were stimulated with CaOx crystals, with siRNA-mediated AT1R or MasR knockdown or pretreatment with Ang Ⅱ, Ang-(1-7), antioxidant Nacetylcysteine (NAC) or autophagy inhibitor 3-methyladenine (3-MA). RAS components, oxidative stress markers, autophagy-related proteins, stone-related proteins and crystal adhesion were detected. In vivo, a mouse CaOx stone model was induced by intraperitoneal glyoxylic acid injection, with adeno-associated virus-mediated AT1R or MasR knockdown. The above indicators and renal crystal deposition were evaluated.

resultsCaOx crystals significantly activated the ACE/Ang Ⅱ/AT1R axis and inhibited the ACE2/Ang-(1-7)/MasR axis in vitro and in vivo, causing intrarenal RAS imbalance. CaOx crystals induced NOX2/4-mediated oxidative stress and AMPK/mTOR-dependent autophagy, which formed a mutually reinforcing loop to upregulate stone-related proteins (OPN, CD44, MCP-1). Activating the ACE/Ang Ⅱ/AT1R axis with Ang Ⅱ exacerbated these pathological changes, while AT1R knockdown alleviated them; conversely, activating the ACE2/Ang-(1-7)/MasR axis with Ang-(1-7) exerted protective effects, whereas MasR knockdown worsened injury. In vivo findings corroborated these results.

conclusionThe ACE/Ang Ⅱ/AT1R axis plays a pathogenic role in CaOx stone formation, whereas the ACE2/Ang-(1-7)/MasR axis exerts a protective effect. Restoring this intrarenal RAS balance represents a promising therapeutic strategy against CaOx stones.

Indexed as

Calcium OxalateKidneyKidney CalculiOxidative StressRenin-Angiotensin SystemAnimalsAutophagyCell LineHumansMaleMiceMice, Inbred C57BLPeptidyl-Dipeptidase ACalcium OxalatePeptidyl-Dipeptidase AAutophagyCaOx stonesOxidative stressThe ACE2/Ang-(1–7)/MasR axisThe ACE/Ang Ⅱ/AT1R axis

Identifiers

PMID42892631

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.