Protective Effect and Mechanism of Bone Morphogenetic Protein-4 on Apoptosis of Human Lens Epithelium Cells under Oxidative Stress

Abstract

Bone morphogenetic proteins (BMPs), a member of the transforming growth factor β (TGF-β) superfamily, are abundant in human ocular tissues and play an important role in lens development. Targeted deletion of BMP-4 in mice results in failure of lens placode formation. Following lens maturation, the formation of senile cataracts is demonstrably associated with free radical-related oxidative stress. Previous studies reported that BMPs play an antiapoptotic role in cells under oxidative stress, and the BMP-4 signal is important in inflammation regulation and homeostasis. BMP-4 evidently suppressed the apoptosis of human lens epithelial cells (HLECS) under oxidative stress induced by H2O2. This protective antiapoptotic effect is partly due to a decrease in caspase-3 activity and reactive oxygen species (ROS) level. Furthermore, the expression of activating transcription factor- (ATF-) 6 and Krüppel-like factor- (KLF-) 6 increased under oxidative stress and decreased after BMP-4 treatment.

Insights into Bone Morphogenetic Protein—(BMP-) Signaling in Ocular Lens Biology and Pathology

“…Work in our laboratory showed that BMP-4 can block TGFβ2-induced EMT in rat lens epithelial explants by suppressing Smad2/3 nuclear translocation [109]. The protective effect of BMP-4 has been further demonstrated in the human lens epithelial cell lines (HLE-B3), where exogenous addition of BMP-4 blocked apoptosis of lens epithelial cells under H 2 O 2 -induced oxidative stress [110]. Intriguingly, small molecule agonists of BMPs, ventromorphins, were unable to suppress TGFβ2-induced lens EMT in rat lens explants, highlighting that not all approaches to promote BMP-signaling can block TGFβ2-induced lens EMT [109].…”

Plant molecules reinforce bone repair: Novel insights into phenol-modified bone tissue engineering scaffolds for the treatment of bone defects

“…Mitochondria, the cellular hub of energy metabolism, plays a central role in regulating intracellular OS. According to available studies, p38/MAPK [ 32 , 33 ] and JNK/ERK [ 33 , 34 ] pathways and relative effectors/regulators (including activating transcription factors (ATFs) [ 35 ], runt-related transcription factor 2 (Runx2) [ 34 ], caspase9 [ 36 ], etc.) were significantly suppressed by OS, resulting in the attenuation of osteoblast differentiation.…”

Reactive Oxygen Species and Eye Aging in Cataracts through Biomolecular Mechanisms

“…The perfect machinery of the human natural lens is an absence of organelles and mitochondria is locked to the epithelial cells, consuming almost ninety percentage of the complete oxygen consumption, practically the lens is hypoxic, calculated to be 3 mmHg (~0.4%); at the end 0.2-2% of the oxygen is destiny to produce superoxide and stimulates the respiratory chain oxidative phosphorylation; meant to be able to describe the new potential solutions [4][5].…”