Kidney Week

Abstract: SA-PO737

Change of Integrin αVβ3 in Glomerular Diseases and Flow Shear Stress

Session Information

• Glomerular Diseases: Podocyte Biology - II
  November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
  Abstract Time: 10:00 AM - 12:00 PM

Category: Glomerular Diseases

• 1304 Glomerular Diseases: Podocyte Biology

Authors

• Kim, Jae seok, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Jae seok Kim,

• Pham, Nghia Thi, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Nghia Thi Pham,

• Kim, Ji-Hee, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Ji-Hee Kim,

• Dang, Bao Thi Ngoc, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Bao Thi Ngoc Dang,

• Eom, Minseob, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Minseob Eom,

• Lee, Jun Young, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Jun Young Lee,

• Yang, Jae Won, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Jae Won Yang,

• Han, Byoung Geun, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Byoung Geun Han,

• Choi, Seung-Ok, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Seung-Ok Choi,

• Cha, Seung-Kuy, Yonsei University Wonju College of Medicine, Wonju, Korea (the Republic of)

Seung-Kuy Cha,

Background

Podocyte and glomerular basement membrane (GBM) are main components of glomerular filtration barrier. Integrins (Itg) play a specific role in the crosstalk of podocyte and GBM under physical stress, but the renal disease-specific expression and context-dependent role of specific Itg remain elusive.

Methods

Here we explored disease-specific integrin (Itg αVβ3) expression using human kidney tissues obtained from the patients with trauma (control), membranous nephropathy (MN), and minimal change disease (MCD), and examined the (patho)physiological role of Itg αVβ3 upon mechanical stress.

Results

In immunohistochemical studies, Itg β3 was exclusively expressed in glomerulus. Itg β3 expression was lower in MN and MCD than that of control, while uPAR and fibronectin, a activator of Itg αVβ3, were higher in MN and MCD. There were no differences in Itg β3, uPAR, and fibronectin between MN and MCD groups (Figure 1). Functional experiments revealed that mechanical forces by fluid shear stress (FSS) upregulated Itg β3 activation and induced actin remodeling without affecting total Itg β3 expression in human podocyte. In addition, FSS increased fibronectin supporting that Itg αVβ3 might be activated in association with fibronectin under FSS (Figure 2).

Conclusion

Taken together, this study demonstrates that Itg αVβ3 may be implicated in the interplay of podocyte and GBM under pathological conditions. In particular, Itg αVβ3 activation by fibronectin is thought to be important step in the role of Itg αVβ3. Our results provide new clues for therapeutic strategies for glomerular diseases.
This work was supported by the National Research Foundation of Korea (NRF) grants (2021R1G1A1004360, 2017R1A5A2015369)

Figure 1. Immunohistochemical studies of human kidney.

Figure 2. Change in the interaction of podocyte-glomerular basement membrane under flow shear stress (FSS).

Funding

• Government Support – Non-U.S.