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Abstract: SA-PO766

Identification of a Mechanosensor in Juxtaglomerular Cells for the Regulation of Renin Synthesis and Secretion

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Wei, Jin, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Zhang, Jie, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Yadav, Nikita S., USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Chan, Jenna, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Patel, Kshama, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Thalakola, Anish Reddy, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Patel, Ridham, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Attalla, Fady George, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Meredith, Garrett Dale, USF Health Morsani College of Medicine, Tampa, Florida, United States
  • Liu, Ruisheng, USF Health Morsani College of Medicine, Tampa, Florida, United States
Background

Juxtaglomerular (JG) cells are a group of specialized vascular smooth muscle (VSM) cells but distinguished from VSM cells by the synthesis and secretion of renin. However, the intracellular mechanisms of renin release from JG remain elusive.

Methods

We performed single-cell RNA seq on a total of 9815 cells that were derived from renal cortex tissue of C57BL/6J mice.

Results

Unbiased clustering analysis demonstrated 12 distinct cell clusters. In particular, a cluster consisting of 284 cells was identified as VSM cells by distinct expression of Acta2 (α-smooth muscle actin). Moreover, based on the co-expression of Ren1 (renin), 34 JG cells were further distinguished from this cluster of VSM cells. We profiled the transcriptome of these JG cells and correlated it with Ren1. The top 5 genes that were most positively correlated with Ren1 expression were Nr2f1, Akr1b7, Smim15, Gng11, and Sdc1. We also compared the transcriptome between JG cells and VSM cells. The top 5 genes that were most differentially expressed in JG cells vs. VSM cells were Ren1, Sfrp2, Akr1b7, Fam46a, and Sdc1. Thus, Akr1b7 and Sdc1 could be potential candidate genes that participate in the control of Ren1 expression in JG cells. In the present study, we examined the role of Sdc1 (syndecan-1) in the regulation of renin synthesis and secretion in response to perfusion pressure changes with both in vitro model of isolated/perfused afferent arteriole (Af-Art) and in vivo model of 2 kidneys 1 clip (2K1C). We found that low perfusion pressure through Af-Art increased Ren1 mRNA expression by 140.7±24.8% while high perfusion pressure decreased the expression by 66.2±13.1% compared to normal perfusion pressure in WT mice. However, the perfusion pressure alteration-induced changes in Ren1 expression were significantly attenuated in SDC1KO mice (n=4-5; p<0.05). Additionally, 2K1C increased renin expression in low-pressure kidney by 163.3±48.7%, plasma renin and Ang II concentrations by 118.2±61.4% and 162.8±50.2%, and mean arterial pressure by 31.6±5.7 mmHg. However, the 2K1C-induced changes were significantly reduced in SDC1KO mice (n=5-7; p<0.01).

Conclusion

In conclusion, this study demonstrates that syndecan-1 is a key mechano-sensor in JG cells that regulates the renin synthesis and secretion.

Funding

  • Other NIH Support