Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral obstruction associated apoptosis and renal interstitial fibrosis.
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.
Kidney Institute and Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Shuqin
S
Mei
Kidney Institute and Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Lin
L
Li
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Qingqing
Q
Wei
Kidney Institute and Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.|Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Jielu
J
Hao
Department of Pharmacology and Toxicology, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.
Yunchao
Y
Su
Kidney Institute and Department of Nephrology, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, China.
Changlin
C
Mei
Department of Cellular Biology and Anatomy, Medical College of Georgia at Augusta University and Charlie Norwood VA medical Center, Augusta, Georgia, USA.|Department of Nephrology, The Second Xiangya Hospital of Central South University, Changsha, China.
Zheng
Z
Dong
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism; D005355:Fibrosis; D007687:Kidney Tubules, Proximal / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D014524:Urethral Obstruction / Q000235:genetics* / Q000473:pathology*; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000172:deficiency*; D051028:bcl-2-Associated X Protein / Q000172:deficiency*
D050998:bcl-2 Homologous Antagonist-Killer Protein; D051028:bcl-2-Associated X Protein; D003094:Collagen