Kidney Week

Abstract: TH-PO932

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

Session Information

• Molecular Mechanisms of CKD - I
  October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: CKD (Non-Dialysis)

• 1903 CKD (Non-Dialysis): Mechanisms

Authors

• Choi, Dae Eun, Chungnam National University, Daejeon, Korea (the Republic of)

Dae Eun Choi,

• Chang, Yoon-Kyung, The Catholic University of Korea, Daejeon, Korea (the Republic of)

Yoon-Kyung Chang,

• Choi, Hyunsu, Daejeon St. Mary's Hospital, Daejeon, Korea (the Republic of)

Hyunsu Choi,

• Jeong, Jin young, Chungnam National University, Daejeon, Korea (the Republic of)

Jin young Jeong,

• Jeon, Jae wan, Asan Medical Center, Seoul, Korea (the Republic of)

Jae wan Jeon,

• Na, Ki Ryang, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Ki Ryang Na,

• Ham, Youngrok, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Youngrok Ham,

• Lee, Jiwon M., Chungnam National University, Daejeon, Korea (the Republic of)

Jiwon M. Lee,

• Lee, Kang Wook, Chungnam National University Hospital, Daejeon, Korea (the Republic of)

Kang Wook Lee,

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.