Kidney Week

Abstract: SA-PO683

The Role of Myocardin-Related Transcription Factor-Serum Response Factor Signaling in Peritoneal Mesothelial Cells

Session Information

• Home Dialysis - II
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Dialysis

• 802 Dialysis: Home Dialysis and Peritoneal Dialysis

Authors

• Kaikoi, Daichi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Daichi Kaikoi,

• Sakai, Norihiko, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Norihiko Sakai,

• Yamamura, Yuta, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Yuta Yamamura,

• Sako, Keisuke, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Keisuke Sako,

• Horikoshi, Keisuke, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Keisuke Horikoshi,

• Yuasa, Takahiro, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Takahiro Yuasa,

• Minami, Taichiro, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Taichiro Minami,

• Nakagawa, Shiori, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Shiori Nakagawa,

• Oshima, Megumi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Megumi Oshima,

• Kitajima, Shinji, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Shinji Kitajima,

• Toyama, Tadashi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Tadashi Toyama,

• Hara, Akinori, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Akinori Hara,

• Shimizu, Miho, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Miho Shimizu,

• Iwata, Yasunori, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Yasunori Iwata,

• Wada, Takashi, Kanazawa Daigaku, Kanazawa, Ishikawa, Japan

Takashi Wada,

Background

Peritoneal membrane failure is a critical complication of long-term peritoneal dialysis treatment. Peritoneal fibrosis has been known to be involved in the development of peritoneal membrane failure. Therefore, clarifying the mechanisms of peritoneal fibrosis is important. Thus far, myocardin-related transcription factor (MRTF) -serum response factor (SRF) signaling is known to drive the development of various fibrosis. Focal adhesion (FA) and lysyl oxidase (LOX) family mediating collagen cross-linking are also known to contribute to the development of organ fibrosis. However, the involvement of MRTF-SRF signaling in the expression of FA components and LOX family in peritoneal fibrosis is unclear. In this study, we investigated the contribution of MRTF-SRF signaling to the expression of FA components and LOX family using peritoneal mesothelial cells (PMC).

Methods

Mouse primary PMCs were stimulated with transforming growth factor (TGF)-β₁. Then, the expressions of α₁ chain of type I procollagen (ColIα₁), FA components and LOX family were evaluated. In addition, the effects of MRTF-SRF signal on their expressions were evaluated in TGF-β₁-stimulated PMCs treated with siRNA targeting MRTF-A/-B or MRTF-SRF inhibitor (CCG-1423).

Results

TGF-β₁ induced the expression of ColIα₁, LOX family and FA components (integrins and integrin linked kinase) in PMCs. Their expressions were reduced with siRNAs targeting MRTF-A/-B. In addition, the expressions of FA components were also reduced with CCG-1423. Taken together, TGF-β₁ induced the expression of Col1α₁, LOX family and FA components dependent on MRTF-SRF signaling in PMCs.

Conclusion

MRTF-SRF signaling may contribute to the development of peritoneal fibrosis through TGF-β₁-induced FA components and LOX family in PMCs.