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Abstract: TH-PO932

Inactivation of KLHL3 Kelch Like Family Member 3 Ameliorates Renal Fibrosis in Unilateral Ureteral Obstructive Mice

Session Information

Category: CKD (Non-Dialysis)

  • 1903 CKD (Non-Dialysis): Mechanisms

Authors

  • Choi, Dae Eun, Chungnam National University, Daejeon, Korea (the Republic of)
  • Chang, Yoon-Kyung, The Catholic University of Korea, Daejeon, Korea (the Republic of)
  • Choi, Hyunsu, Daejeon St. Mary's Hospital, Daejeon, Korea (the Republic of)
  • Jeong, Jin young, Chungnam National University, Daejeon, Korea (the Republic of)
  • Jeon, Jae wan, Asan Medical Center, Seoul, Korea (the Republic of)
  • Na, Ki Ryang, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
  • Ham, Youngrok, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
  • Lee, Jiwon M., Chungnam National University, Daejeon, Korea (the Republic of)
  • Lee, Kang Wook, Chungnam National University Hospital, Daejeon, Korea (the Republic of)
Background

KLHL3 kelch like family member 3 (KLHL3) regulate some electrolyte in kidney tubules. In human, the mutation of KLHL3 induce hypertension, characterized by pseudoaldosteronism (decreasing aldosterone). We evaluated whether the KLHL3 could be fair target of RAAS inhibition, resulting in inhibition of renal fibrosis in unilateral ureteral obstructed (UUO) mice.

Methods

10-week-old male B6 mice background KLHL3 KO mice and wild type mice were divided into 4 groups; wild, KLHL3 KO, wild with UUO, and KLHL3 KO with UUO. Mice were sacrificed at 7 days after surgery and kidney tissue were collected. Real time RT-PCR, western blot and immunohistochemistry for molecular study and H&E stain and PAS stain for histologic examination were performed.

Results

KLHL3 KO with UUO mice showed improvement of renal cell survival, renal function, and pathologic damage compared to wild type UUO mice. Wild type with UUO kidney showed decrease of renal expression of KLHL3 and WNK4, and increase of renin and angiotensin I receptor, compared to sham mice. However, KLHL3 KO with UUO reduced the renal expression of renin, angiotensin I receptor, alpha-SMA, collagen IV, and TGF-ß in UUO kidney, compared to wild type with UUO mice.

Conclusion

KLHL3 KO ameliorate renal fibrosis in UUO kidney via inhibition or renin angiotensin system.

Funding

  • Government Support - Non-U.S.