Kidney Week

Abstract: SA-PO980

Exosomes from Activated Kidney Fibroblast Stimulate Transcription of PlGF on Endothelial Cells

Session Information

• Hypertension and CVD: Mechanisms - II
  October 27, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

• 1403 Hypertension and CVD: Mechanisms

Authors

• Kato, Noritoshi, Nagoya University Graduate School of Medicine, Nagoya, Japan

Noritoshi Kato,

• Nishio, Fumitoshi, Nagoya University, Nagoya, Aichi-KEN, Japan

Fumitoshi Nishio,

• Funahashi, Yoshio, Nagoya University, Nagoya, Aichi-KEN, Japan

Yoshio Funahashi,

• Ishimoto, Takuji, Nagoya University Graduate School of Medicine, Nagoya, Japan

Takuji Ishimoto,

• Kosugi, Tomoki, Nagoya University Graduate School of Medicine, Nagoya, Japan

Tomoki Kosugi,

• Tsuboi, Naotake, Nagoya University Graduate School of Medicine, Nagoya, Japan

Naotake Tsuboi,

• Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan

Shoichi Maruyama,

Background

Exosomes are small membrane vesicles that contain host cell’s proteins, mRNAs, and microRNAs. The body of evidence revealed that these contents were biologically active and had roles in intracellular communication. On the other hand, it is well known that CKD patients are at risk of cardiovascular diseases, but the mechanism of this distant organ crosstalk is not fully understood. Recently, placental growth factor (PlGF) received attention in pathogenesis of cardio-renal syndrome (CRS). Under the hypothesis that exosomes are involved in pathophysiology of CRS, the aim of this study is to explore the role of exosomes from kidney fibroblasts, which actively proliferate in diseased kidney, on vascular endothelial cells.

Methods

Clinical samples; HUVECs were stimulated by serum exosomes from stage G5 CKD patients and healthy donor. Exosomes tracking; Activated kidney fibroblasts were isolated from unilateral ureteral obstruction (UUO) mice kidney. These exosomes were labeled by microRNA of C. elegance (Cel-miR-39), then labeled Exosomes were injected to the mice through tail vein. Effects of exosomes on endothelial cells; We purified exosomes from culture media of TGF-b stimulated kidney fibroblasts cell line (NRK-49f), and then primary culture of vascular endothelial cells (RAOEC) was stimulated using these exosomes. By qPCR, we evaluated the expression of PlGF genes.

Results

(1) Not only the serum but also exosomes from CKD stage G5 patients stimulated PlGF expression on HUVECs. (2) Injected labeled exosomes from activated kidney fibroblast distributed mainly in lung, liver, and aorta. (3) RAOEC stimulated with exosomes form TGF-b activated rat kidney fibroblast (RAOEC-T) showed higher expression of PlGF than control (RAOEC-C).

Conclusion

So far, CRS is considered to be caused by uremic factor, RAS system, chronic inflammation, and so on. From this study, both serum and exosomes from CKD patients stimulated PlGF transcription on endothelial cells. Exosomes from activated kidney fibloblast had same tendency. We speculated that exosomes from diseased kidney have some roles in atherosclerotic change by modulating the expression of PlGF on endothelial cells. Farther studies are needed to elucidate the degree of contribution to CRS.