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. 2017 Mar 20:7:44892.
doi: 10.1038/srep44892.

Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis

Shuqin Mei  1   2 , Lin Li  1   2 , Qingqing Wei  2 , Jielu Hao  1   2 , Yunchao Su  3 , Changlin Mei  1 , Zheng Dong  2   4
Affiliations

Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis

Shuqin Mei et al. Sci Rep. .

Abstract

Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO. The results indicate that the intrinsic pathway of apoptosis contributes significantly to the tubular apoptosis and renal interstitial fibrosis in kidney diseases.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Establishment of proximal tubule-specific Bax and Bak-double knockout (PT-Bax/Bak-DK) mouse model.
(A) Schematics showing the breeding protocol for generating PT-Bax/Bak-DK mice by crossing Bax(flox/flox)Bak(WT/WT) XCREX mice with Bax(WT/WT)Bak(flox/flox)XY mice. (B) Immunoblot analysis of renal cortical tissues to confirm the decreases in Bax and Bak expression in PT-Bax/Bak-DK mice.
Figure 2
Figure 2. UUO-associated renal tubular apoptosis is alleviated in PT-Bax/Bak-DK mice.
PT-Bax/Bak-DK and littermate WT mice (10–12 weeks old) were subjected to UUO or sham surgery, and then sacrificed to harvest the kidneys at 4, 7 and 14 days, respectively. (A) Representative images of TUNEL staining. (B) Quantification of TUNEL positive cells in kidney tissues. Data were expressed as mean ± SD. *P < 0.05, significant difference between WT and PT-Bax/Bak-DK groups.
Figure 3
Figure 3. UUO-associated collagen deposition in kidney tissues is reduced in PT-Bax/Bak-DK mice.
PT-Bax/Bak-DK and littermate WT mice (10–12 weeks old) were subjected to UUO or sham surgery, and then sacrificed to harvest the kidneys at 4, 7 and 14 days for paraffin-embedding and Masson’s trichrome staining. (A) Representative images of Masson’s trichrome staining. (B) Quantification of Masson’s trichrome positive areas in whole kidney tissue fields. Data were expressed as mean ± SD. *P < 0.05, significant difference between WT and PT-Bax/Bak-DK groups.
Figure 4
Figure 4. UUO-associated expression of fibrosis and extracellular matrix markers in kidney tissues is suppressed in PT-Bax/Bak-DK mice.
PT-Bax/Bak-DK and littermate WT mice (10–12 weeks old) were subjected to UUO or sham surgery, and then sacrificed to harvest the kidneys at 4, 7 and 14 days. (A) Immunoblot analysis of kidney tissues for fibronectin, α-SMA, collagen IV and cyclophilin B (loading control). (B) Densitometry analysis of the immunoblot signals of fibronectin, α-SMA, and collagen IV as a ratio to cyclophilinB. Data were expressed as mean ± SD. *P < 0.05, significant difference between WT and PT-Bax/Bak-DK groups.
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References

    1. Fox C. et al.. Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease. Sci Rep 6, 20101, doi: 10.1038/srep20101 (2016). - DOI - PMC - PubMed
    1. Wouters O. J., O’Donoghue D. J., Ritchie J., Kanavos P. G. & Narva A. S. Early chronic kidney disease: diagnosis, management and models of care. Nat Rev Nephrol 11, 491–502, doi: 10.1038/nrneph.2015.85 (2015). - DOI - PMC - PubMed
    1. Wang L. et al.. Induction of secondary apoptosis, inflammation, and lung fibrosis after intratracheal instillation of apoptotic cells in rats. Am J Physiol Lung Cell Mol Physiol 290, L695–L702, doi: 10.1152/ajplung.00245.2005 (2006). - DOI - PubMed
    1. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 35, 495–516, doi: 10.1080/01926230701320337 (2007). - DOI - PMC - PubMed
    1. Wei Q., Dong G., Chen J. K., Ramesh G. & Dong Z. Bax and Bak have critical roles in ischemic acute kidney injury in global and proximal tubule-specific knockout mouse models. Kidney Int 84, 138–148, doi: 10.1038/ki.2013.68 (2013). - DOI - PMC - PubMed

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