Effect of exogenous TGF-β1 on the cadmium-induced nephrotoxicity by inhibiting apoptosis of proximal tubular cells through PI3K-AKT-mTOR signaling pathway.
Heavy metal polluted soils have been a serious problem for the global ecological balance and people's health. Cadmium (Cd), one of the heavy metals, could induce apoptosis of proximal tubular cells in many experimental models and lead to damage the human kidney. Here, we reported a potent chemokine TGF-β1 which could ameliorate cadmium-induced nephrotoxicity. Interestingly, western blotting and TUNEL staining assays indicated that PI3K-AKT-mTOR signaling pathway was involved in the protective mechanism of TGF-β1 in vitro and in vivo. Moreover, TGF-β1 could alleviate Cd-induced nephrotoxicity by inhibiting apoptosis of proximal tubular cells through detecting the level of caspase 3, 8 and 9. Therefore, up-regulation of exogenous TGF-β1 may be a potential strategy to reverse cadumium-induced nephrotoxicity.
College of Life Sciences, Anqing Normal University, Anqing, Anhui 246133, China; Anhui Key Laboratory for Research and Ecological Conservation on Anhui, Southwest of Biodiversity, Anqing 246011, Anhui, China.
Minyi
M
Huang
School of Pharmacy, Second Military Medical University, Shanghai, China.
Li
L
Su
College of Life Sciences, Anqing Normal University, Anqing, Anhui 246133, China; Anhui Key Laboratory for Research and Ecological Conservation on Anhui, Southwest of Biodiversity, Anqing 246011, Anhui, China.
Limin
L
Yang
College of Life Sciences, Anqing Normal University, Anqing, Anhui 246133, China; Anhui Key Laboratory for Research and Ecological Conservation on Anhui, Southwest of Biodiversity, Anqing 246011, Anhui, China.
Liangliang
L
Zhu
College of Life Sciences, Anqing Normal University, Anqing, Anhui 246133, China.
Zhaowen
Z
Liu
College of Life Sciences, Anqing Normal University, Anqing, Anhui 246133, China; Anhui Key Laboratory for Research and Ecological Conservation on Anhui, Southwest of Biodiversity, Anqing 246011, Anhui, China. Electronic address: duanreny@163.com.
Renyan
R
Duan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002104:Cadmium / Q000633:toxicity*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D002104:Cadmium; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020123:Sirolimus; D058570:TOR Serine-Threonine Kinases; D053773:Transforming Growth Factor beta1
Apoptosis; C57bl/6J mice; Cadmium; HK-2 cells; TGF-β1