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Apelin-13 Pretreatment Attenuates Age-Associated Renal Fibrotic Remodeling Following I/R Injury

Won-Seok Oh, Sang Gon Lee, H.-T. Kim, Ji-Hyun Moon and 6 more

Biomedicines | Sep 10, 2026

Abstract

Abstract

Background/Objectives: Aging is a major risk factor that exacerbates acute kidney injury (AKI) and subsequent renal fibrosis. However, age-related factors contributing to post-AKI fibrotic remodeling remain underexplored. This study aimed to investigate the protective potential of apelin, an endogenous peptide, in mitigating post-AKI renal fibrosis in aged mice. Methods: A mouse model of AKI was established in 8-week-old and 19-month-old male C57BL/6 mice by clamping the left renal artery for 40 min, followed by reperfusion and euthanasia 2 weeks post-ischemia. To evaluate the protective effect of apelin pretreatment, the 19m-APLN group received intraperitoneal apelin administration (25 μg/kg/day) for 2 weeks prior to AKI induction. The effects of apelin on renal fibrosis were evaluated using renal function tests (blood urea nitrogen, serum creatinine levels), histological analysis, and Western blotting. Results: The 19m-AKI group exhibited more severe renal damage and interstitial fibrosis, along with a marked reduction in apelin and APLNR expression compared to the 8wk-AKI group. Apelin-13 pretreatment attenuated renal injury and fibrotic remodeling in aged mice, with reduced collagen deposition accompanied by lower pro-TGF-β1 expression and SMAD3 phosphorylation. Conclusions: These results highlight the protective role of apelin against age-related exacerbation of post-AKI renal fibrosis, suggesting that prophylactic Apelin-13 administration may attenuate post-I/R renal injury and fibrotic remodeling in aged kidneys.

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Authors

Researchers on this paper

Won-Seok Oh

first | Chungnam National University

Sang Gon Lee

middle | Chungnam National University

H.-T. Kim

middle | Korea Basic Science Institute | ORCID 0000-0003-2407-5448

Ji-Hyun Moon

middle | Konyang University

Ah-La Choi

middle | Konyang University

Seung Yun Han

middle | Cheongju University | ORCID 0000-0002-7055-6341

Do Kyung Kim

middle | Konyang University | ORCID 0000-0001-6655-7061

Nam Seob Lee

middle | Konyang University

Young Gil Jeong

middle | Konyang University

Geum-Lan Hong

last | Chungnam National University | ORCID 0000-0001-6680-5379

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Citation

BibTeX

@article{Oh2026Apelin,
  title = {Apelin-13 Pretreatment Attenuates Age-Associated Renal Fibrotic Remodeling Following I/R Injury},
  author = {Won-Seok Oh and Sang Gon Lee and H.-T. Kim and Ji-Hyun Moon and Ah-La Choi and Seung Yun Han and Do Kyung Kim and Nam Seob Lee and Young Gil Jeong and Geum-Lan Hong},
  journal = {Biomedicines},
  year = {2026},
  doi = {10.3390/biomedicines14092033},
  url = {https://doi.org/10.3390/biomedicines14092033}
}

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