Abstract: SA-PO295

Knockdown of Peroxiredoxin V (Prdx V) Exacerbates Unilateral Ureteral Obstruction-Induced Renal Fibrosis

Session Information

Category: Cell Biology

  • 204 Extracellular Matrix Biology, Fibrosis, Cell Adhesion

Authors

  • Choi, Hoon In, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Lee, Tae-Hoon, School of Dentistry, Chonnam National University, Gwangju, Korea (the Republic of)
  • Park, Jung Sun, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Kim, Donghyun, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Bae, Eun Hui, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Ma, Seong Kwon, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
  • Kim, Soo Wan, Chonnam National University Medical School, Gwangju, Korea (the Republic of)
Background

Renal fibrosis is closely associated with chronic inflammation. Peroxiredoxin V (Prdx V), an atypical 2-Cys member of the Prdxs family, functions as anti-inflammatory effector as well as a thiol-dependent peroxidase in its catalytic cysteine-dependent manner. Recently, we demonstrated that overexpression of Prdx V attenuate TGF-β induced fibrosis in NRK49F cells. However, the relevance of Prdx V to renal pathobiology has not been fully characterized and the underlying mechanism remains poorly understood.

Methods

To investigate the role of Prdx V in renal fibrosis, we used a transgenic mouse model with PrdxV siRNA expression controlled by U6 promoter (C57BL/6J-Tg(U6-PrdxVsi)1Thlee/Krb; Prdx Vsi mice). For in vivo experiments, both Prdx Vwt and Prdx Vsi mice were divided to each two groups (Control vs UUO group, each n = 8). The UUO groups were subjected to unilateral ureteral obstruction (UUO) by ligation of the left ureter for seven days. The control groups were performed to the same treatment for seven days, with the exception of the ligature.

Results

Consistent with our previous data, the protein expression of Prdx V was less in UUO group kidney than the control group kidney. Compared with UUO-induced Prdx Vwt mouse kidney, UUO-induced Prdx Vsi mouse kidney had more stained by TGF-β and α-SMA which is gradually increased by fibrosis progression. Knockdown of Prdx V in kidney exacerbated the UUO-induced increase in fibrotic marker expression, such as TGF-β, α-SMA, and vimentin, and also, augmented the reduction of E-cadherin, an epithelial marker as well as the increase in oxidative stress, such as nitrotyrosine and lipid peroxidation. Furthermore, we observed the activation of canonical and non-canonical TGF- β signal pathway, resulting in renal fibrosis progression. In canonical TGF- β signals, the increase of Smad4 that plays a critical role in nucleocytoplasmic shuttling of Smad2/3 is remarkable in UUO-induced Prdx Vsi mouse kidney. In non-canonical TGF-β signals, phosphorylation of Stat3 is accentuated in UUO-induced Prdx Vsi mouse kidney consistent with our earlier in vitro data.

Conclusion

Prdx V is an anti-fibrotic effector that sustains renal physiology. Negative regulation mechanism of TGF-β signaling by Prdx V could be a therapeutic target to protect renal fibrosis.