Mechanism of Mitophagy to Protect Yak Kidney from Hypoxia-Induced Fibrosis Damage by Regulating Ferroptosis Pathway DOI Creative Commons
Xuefeng Bai,

Hongqin Lu,

Rui Ma

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 556 - 556

Published: April 9, 2025

Renal fibrosis is a critical pathological feature of various chronic kidney diseases, with hypoxia being recognized as an important factor in inducing fibrosis. Yaks have long inhabited high-altitude hypoxic environments and do not exhibit fibrotic damage under hypoxia. However, the underlying protective mechanisms remain unclear. This study compared renal tissue structure collagen volume between low-altitude cattle yaks, revealing that yaks possess significantly higher number tubules than cattle, though showed no significant difference. Under treatment, we observed induced but did show effect suggesting adaptation may anti-fibrotic effect. Further investigation demonstrated upregulation P-AMPK/AMPK, Parkin, PINK1, LC3Ⅱ/Ⅰ, BECN1, alongside downregulation P-mTOR/mTOR yak kidneys. Additionally, hypoxia-induced tubular epithelial cells (RTECs) increased expression mitophagy-related proteins, mitochondrial membrane depolarization, lysosomes, indicating induces mitophagy. By regulating mitophagy pathway through drugs, found hypoxia, activation upregulated E-cadherin protein while downregulating Vimentin, α-SMA, Collagen I, Fibronectin. Simultaneously, there was increase SLC7A11, GPX4, GSH levels, decrease ROS, MDA, Fe2⁺ accumulation. Inhibition produced opposite effects on cellular markers. studies identified ferroptosis key mechanism promoting Moreover, models, reduced accumulation Fe2⁺, thereby alleviating ferroptosis-induced These findings suggest protects from by activating to inhibit pathway.

Language: Английский

Hypoxia Regulates the Proliferation and Apoptosis of Coronary Artery Smooth Muscle Cells Through HIF-1α Mediated Autophagy in Yak DOI Creative Commons

Shanshan Yang,

Yan Cui, Rui Ma

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(2), P. 256 - 256

Published: Feb. 10, 2025

Cell proliferation and migration mediated by hypoxia-inducible factor-1α (HIF-1α) are important processes of hypoxic cardiac vascular remodeling. HIF-1α also regulates the physiological adaptation coronary artery in yak heart, but potential mechanism remains to be completely elucidated. In this study, increased with age hypoxia time. vitro analysis showed that can promote smooth muscle cells (CASMCs). Meanwhile, plays an role regulation under hypoxia. Autophagy cell participate plateau animals. Here, level autophagy significantly arteries was regulated HIF-1α-mediated addition, could mediate effect on CASMCs. summary, results revealed increase heart thickening increases migration, mainly achieved through hypoxia-mediated HIF-1α-regulated autophagy. These contribute understanding how adapts life a environment.

Language: Английский

Citations

0
Mechanism of Mitophagy to Protect Yak Kidney from Hypoxia-Induced Fibrosis Damage by Regulating Ferroptosis Pathway DOI Creative Commons
Xuefeng Bai,

Hongqin Lu,

Rui Ma

et al.

Biomolecules, Journal Year: 2025, Volume and Issue: 15(4), P. 556 - 556

Published: April 9, 2025

Renal fibrosis is a critical pathological feature of various chronic kidney diseases, with hypoxia being recognized as an important factor in inducing fibrosis. Yaks have long inhabited high-altitude hypoxic environments and do not exhibit fibrotic damage under hypoxia. However, the underlying protective mechanisms remain unclear. This study compared renal tissue structure collagen volume between low-altitude cattle yaks, revealing that yaks possess significantly higher number tubules than cattle, though showed no significant difference. Under treatment, we observed induced but did show effect suggesting adaptation may anti-fibrotic effect. Further investigation demonstrated upregulation P-AMPK/AMPK, Parkin, PINK1, LC3Ⅱ/Ⅰ, BECN1, alongside downregulation P-mTOR/mTOR yak kidneys. Additionally, hypoxia-induced tubular epithelial cells (RTECs) increased expression mitophagy-related proteins, mitochondrial membrane depolarization, lysosomes, indicating induces mitophagy. By regulating mitophagy pathway through drugs, found hypoxia, activation upregulated E-cadherin protein while downregulating Vimentin, α-SMA, Collagen I, Fibronectin. Simultaneously, there was increase SLC7A11, GPX4, GSH levels, decrease ROS, MDA, Fe2⁺ accumulation. Inhibition produced opposite effects on cellular markers. studies identified ferroptosis key mechanism promoting Moreover, models, reduced accumulation Fe2⁺, thereby alleviating ferroptosis-induced These findings suggest protects from by activating to inhibit pathway.

Language: Английский

Citations

0