Evidence map›Paper›PMID 42726771›Full record

ArticlePloS one2026

A dual role of AcSDKP in chronic kidney disease: Targeting pericyte-driven fibrosis and vascular repair via VEGF/FGFR1 while eliciting a compensatory FGFR1 upregulation in apoptotic tubular cells.

Shiyi Zhu, Lingli Shi, Linlin Huang, Ningxun Cui, Ruyue Chen, Lu Jiang, Annan Zhang, Yunyun Xu, Xiaozhong Li

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in PloS one, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Shiyi ZhuKidney Pathology and Immunology Laboratory, Pediatric Clinical Research Institute of Soochow University, Pediatric Clinical Medical College of Soochow University, Children's Hospital of Soochow University, Soochow, China.
Lingli ShiPediatric Department, Suzhou Municipal Hospital & Department of Nephrology and Immunology, Children's Hospital of Soochow University, Soochow, China.
Linlin HuangKidney Pathology and Immunology Laboratory, Pediatric Clinical Research Institute of Soochow University, Pediatric Clinical Medical College of Soochow University, Children's Hospital of Soochow University, Soochow, China.
Ningxun CuiKidney Pathology and Immunology Laboratory, Pediatric Clinical Research Institute of Soochow University, Pediatric Clinical Medical College of Soochow University, Children's Hospital of Soochow University, Soochow, China.
Ruyue ChenDepartment of Nephrology and Immunology, Children's Hospital of Soochow University, Soochow, China.
Lu JiangDepartment of Nephrology and Immunology, Children's Hospital of Soochow University, Soochow, China.
Annan ZhangElectronic Information School of Wuhan University, Wuhan, China.
Yunyun XuPediatric Clinical Research Institute of Soochow University, Pediatric Clinical Medical College of Soochow University, Children's Hospital of Soochow University, Soochow, China.
Xiaozhong LiPediatric Clinical Research Institute of Soochow University, Pediatric Clinical Medical College of Soochow University, Department of Nephrology and Immunology, Children's Hospital of Soochow University, Soochow, China.ORCID https://orcid.org/0000-0002-2911-7814

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundRenal interstitial fibrosis and peritubular capillary (PTC) rarefaction drive the progression of chronic kidney disease (CKD). While N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous anti-fibrotic peptide, its specific effects on pericyte-endothelial crosstalk and tubular epithelial survival remain controversial.

methodsWe employed a self-controlled unilateral aristolochic acid (AA)-induced CKD mouse model to evaluate the time-sensitive efficacy of AcSDKP. In vitro, primary murine pericytes, human tubular epithelial cells (HK-2), and endothelial cells were utilized. Functional mechanisms were dissected using VEGF ELISA, RNA-sequencing, and targeted FGFR1 siRNA knockdown.

resultsIn vitro, AcSDKP potently suppressed TGF-β1-induced pericyte-to-myofibroblast transition (PMT) and robustly restored pericyte-derived VEGF secretion, thereby rescuing endothelial tubulogenesis. In vivo, early AcSDKP intervention (Week 3) significantly mitigated fibrosis, preserved capillary integrity, and improved systemic renal function (BUN/SCr), whereas late intervention (Week 4) was less effective. Transcriptomics identified the VEGF/FGFR1 axis as a primary target of AcSDKP. However, in AA-injured HK-2 cells, AcSDKP paradoxically exacerbated apoptosis despite upregulating FGFR1. Subsequent siRNA knockdown revealed that silencing FGFR1 drastically worsened apoptosis, proving that endogenous FGFR1 upregulation is a compensatory survival response. AcSDKP's epithelial toxicity is fundamentally FGFR1-independent, driven instead by its concurrent inhibition of the Akt survival pathway.

conclusionAcSDKP exerts a compartment-specific dual role in CKD. It is a potent vascular protector that halts PMT and promotes VEGF-driven endothelial repair, but acts as a pro-apoptotic stressor in severely damaged tubules. Its clinical translation necessitates early-stage intervention and optimized delivery strategies to maximize vascular benefits while mitigating epithelial toxicity.

Indexed as

Kidney TubulesPericytesReceptor, Fibroblast Growth Factor, Type 1Renal Insufficiency, ChronicVascular Endothelial Growth Factor AAnimalsApoptosisAristolochic AcidsCell LineDisease Models, AnimalEpithelial CellsFibrosisHumansMaleMiceMice, Inbred C57BLaristolochic acid IAristolochic AcidsFGFR1 protein, humanFgfr1 protein, mousegoralatideOligopeptidesReceptor, Fibroblast Growth Factor, Type 1Vascular Endothelial Growth Factor A

Identifiers

PMID42726771
PMCPMC13567759

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.