ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: SA-PO115

Transplanted Senescent Renal Tubular-Like Cells Induce Renal Microvascular Injury

Session Information

Category: Acute Kidney Injury

  • 103 AKI: Mechanisms

Authors

  • Kim, Seo Rin, Mayo clinic, Rochester, United States
  • Jiang, Kai, Mayo clinic, Rochester, Minnesota, United States
  • Ferguson, Christopher M., Mayo clinic, Rochester, Minnesota, United States
  • Tang, Hui, Mayo clinic, Rochester, Minnesota, United States
  • Chen, Xiaojun, Mayo clinic, Rochester, Minnesota, United States
  • Zhu, Xiang yang, Mayo clinic, Rochester, Minnesota, United States
  • Hickson, LaTonya J., Mayo clinic, Rochester, Minnesota, United States
  • Tchkonia, Tamara, Mayo Clinic, Rochester, Minnesota, United States
  • Kirkland, James L., Mayo Clinic, Rochester, Minnesota, United States
  • Lerman, Lilach O., Mayo clinic, Rochester, Minnesota, United States
Background

Cellular senescence is characterized by a senescence-associated secretory phenotype (SASP), which reinforces senescence and exerts noxious effects on adjacent cells. Recent studies suggest that transplanting small numbers of senescent cells suffices to provoke tissue inflammation. Several models of kidney disease show increased prevalence of senescent renal cells. We hypothesized that senescent cells can directly augment renal injury.

Methods

Cellular senescence was induced in primary tubular-like cells acquired from pig kidneys by 10Gy of cesium radiation, and 3 weeks later cells were characterized for senescence and SASP markers. Control (CON) or senescent (SEN) renal tubular-like cells were pre-labeled and injected intra-aorta to C57BL/6J mice. Four weeks later, renal oxygenation was studied using magnetic resonance imaging, and function by plasma creatinine level. Renal markers of SASP, fibrosis, and microvascular density were evaluated.

Results

Per flow cytometry, 80-99% renal tubular-like cells were senescent after irradiation. They showed increased mRNA of senescence and SASP markers, SA-ß-gal staining, and cytokines levels secreted in conditioned-medium. Four weeks after injection, cells were detected engrafted in the kidneys with no evidence for rejection. Plasma creatinine and renal tissue hypoxia tended to increase in SEN compared to CON. SEN kidneys were more fibrotic, with fewer CD31+ endothelial cells, and showed upregulation of IL-6 gene expression.

Conclusion

Senescent renal tubular-like cells directly induce renal inflammation, fibrosis, microvascular loss, and hypoxia. These observations suggest a role for cellular senescence in the pathogenesis of kidney injury, and support development of senolytic therapy.

Funding

  • NIDDK Support