Kidney Week

Abstract: TH-PO916

6-BIO Attenuates TGFβ-Induced Fibrosis by Suppression of Transcription Factor AP-1 and SP-1 of Plasminogen Activator Inhibitor Type-1 in the Human Renal Proximal Tubular Epithelial Cells

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

• Park, Jung Sun, Chonnam National University, Gwangju, Korea (the Republic of)

Jung Sun Park,

• Choi, Hoon In, Chonnam National University Medical School, Gwangju, Korea (the Republic of)

Hoon In Choi,

• Kim, Donghyun, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Donghyun Kim,

• Bae, Eun Hui, Chonnam National University Hospital, Gwangju, Korea (the Republic of)

Eun Hui Bae,

• Ma, Seong Kwon, Chonnam National University Medical School, Gwangju, Korea (the Republic of)

Seong Kwon Ma,

• Kim, Soo Wan, Chonnam National University Medical School, Gwangju, Korea (the Republic of)

Soo Wan Kim,

Background

PAI-1 is expressed at high levels in several both acute and chronic kidney diseases, and leading to activation of lung, liver, kidney fibrosis. We investigated whether 6-BIO, a glycogen synthase kinase-3β inhibitor, attenuates fibrosis by PAI-1 inhibition in TGFβ-induced proximal tubular (HK2) cells injury.

Methods

The effects of 6-BIO in TGFβ-induced cell fibrosis were determined using human renal proximal tubular epithelial (HK-2) cells. The effects of TGFβ and 6-BIO on cell viability were determined using EZ-CyTox assays. The protein and mRNA expression of PAI-1, Collagen I, Collagen IV, CTGF, SMAD, PI3K/AKT, MAPK, and NF-κB was determined by semiquantitative immunoblotting and RT-PCR. To study the factors that regulation of PAI-1 expression, we analyzed the promoter activities of transcription factors AP-1 and Sp-1 were determined by luciferase assays.

Results

Treatment of TGFβ increase expression of PAI-1, Collagen I, Collagen IV, and CTGF in HK-2 cells. Furthermore, TGFβ-treatment induces the activation of p-SMAD2/3, SMAD4, p-AKT, p-ERK1/2, p-p38, and p-JNK MAPK signal pathway as well as NF-κB nuclear transactivation. AP-1 and SP-1 promoter luciferase activity is increase by TGFβ treatment. 6-BIO pretreatment decreases PAI-1, Collagen I, Collagen IV, CTGF fibrotic protein expression in TGFβ-induced HK-2 cells. 6-BIO decreases the increased NF-κB nuclear transactivation, p-SMAD2/3, SMAD4, p-AKT, p-ERK1/2, p-p38, and p-JNK MAPK pathway in HK-2 cells. Additionally, pretreatment of 6-BIO attenuates AP-1 and SP-1 promoter activity.

Conclusion

Treatment of 6-BIO may exert anti-fibrotic effect by controlling SMAD, PI3K/AKT, MAPK, and NF-κB signal pathways via inhibition of the transcription factor AP-1 and SP-1 of PAI-1 in TGFβ-treated HK-2 cells.

Funding

• Government Support - Non-U.S.