Differential Analysis of CD146 and Hypoxia-related Factors in Yak (Bos grunniens) and Cattle (Bos taurus) Brain Tissue
WANG Jun1, ZHANG Fan1,2,3, XU Ming-Wei1, HU Jia-Qi1, MA Wei-Qian1, MA Si-Heng1, ZHONG Yan1, CHEN Wei-Ji1, TAN Xiao1, LAN Wen-Lin1, YANG Kun1,2,3,*
1 Life Science and Engineering College, Northwest Minzu University, Lanzhou 730030, China; 2 Gansu Tech Innovation Center of Animal Cell, Lanzhou 730030, China; 3 Biomedical Research Center, Northwest Minzu University, Lanzhou 730030, China
Abstract：Hypoxia at high altitude can cause irreversible damage to brain tissue. By comparing and analyzing the differential expressions of cluster of differentiation 146 (CD146) and hypoxia-related factors—hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), Beclin-1 and cysteine aspartate specific protease 3 (Caspase-3), in different brain tissues between yak (Bos grunniens) and yellow cattle (Bos taurus), this study explored their correlation with brain hypoxia adaptability of yak. Brain tissues (cerebrum, cerebellum, corpora quadrigemina and medulla) of adult yaks and cattle were collected for H&E, PAS, Nissl and Masson staining and immunohistochemical analysis. Based on the results of staining, various parameters were measured, including the proportion of pyramidal cells, Purkinje cell area, the distribution of glycogen accumulation, neuronal distribution and nerve fiber contents. The results showed that the differences in brain tissue between yaks and yellow cattle were mainly concentrated in the cerebellum and medulla, with all parameters in the cerebellum being significantly higher than those in the medulla (P<0.05). For interspecific differences, the average optical density (AOD) in PAS staining and the positive rate in Nissl staining were significantly higher in yak brain tissue than that in yellow cattle (P<0.05), and the proportion of nerve fibers in Masson staining was significantly higher in the yak cerebrum and cerebellum than that in yellow cattle (P<0.05), but significantly lower in the yak medulla and corpora quadrigemina (P<0.05).Immunohistochemical results showed that the differential expressions of CD146 and hypoxia-related factors were mainly in cerebellum and medulla. For inter-regional differences, the expressions of CD146 and hypoxia-related factors in the yak cerebellum were significantly higher than those in the medulla (P<0.05), whereas in yellow cattle, their expressions in the cerebellum were lower than those in the medulla. For interspecific differences, the expressions of CD146, HIF-1α, and VEGF in the yak cerebellum were higher than those in yellow cattle, while the expression trend of Beclin-1 was the opposite, the expressions of CD146 and hypoxia-related factors in the yak medulla were significantly lower than those in yellow cattle (P<0.05). Combined with the biological functions of CD146 and hypoxia-related factors, it was speculated that CD146 might play a role in the adaptation of yak brain to hypoxic environment. This study provides basic data for further exploring the specificity of hypoxia adaptation of yak brain tissue and the regulation mechanism of CD146 and hypoxia-related factors under hypoxia.
王军, 张凡, 徐铭蔚, 胡嘉琦, 马唯倩, 马思恒, 钟妍, 陈伟基, 谈笑, 蓝雯琳, 杨琨. CD146与低氧相关因子在牦牛和黄牛脑组织差异分析[J]. 农业生物技术学报, 2025, 33(12): 2626-2638.
WANG Jun, ZHANG Fan, XU Ming-Wei, HU Jia-Qi, MA Wei-Qian, MA Si-Heng, ZHONG Yan, CHEN Wei-Ji, TAN Xiao, LAN Wen-Lin, YANG Kun. Differential Analysis of CD146 and Hypoxia-related Factors in Yak (Bos grunniens) and Cattle (Bos taurus) Brain Tissue. 农业生物技术学报, 2025, 33(12): 2626-2638.
[1] Abbas M, Sharma G, Dambire C, et al.2022. An oxygen-sensing mechanism for angiosperm adaptation to altitude[J]. Nature, 606(7914): 565-569. [2] Aburto M R, Cryan J F.2024. Gastrointestinal and brain barriers: Unlocking gates of communication across the microbiota-gut-brain axis[J]. Nature Reviews Gastroenterology Hepatology, 21(4): 222-247. [3] Alsbrook D L, Di N M, Bhatia K, et al.2023. Neuroinflammation in acute ischemic and hemorrhagic stroke[J]. Current Neurology and Neuroscience Reports, 23(8): 407-431. [4] Burtscher J, Mallet R T, Burtscher M, et al.2021. Hypoxia and brain aging: Neurodegeneration or neuroprotection?[J]. Ageing Research Reviews. 68(7): 101343-101351 [5] Huang Z Y, Teng W B, Yao L X, et al.2024. mTOR signaling pathway regulation HIF-1 α effects on LPS induced intestinal mucosal epithelial model damage[J]. BMC Molecular and Cell Biology, 25(1): 13-26. [6] Imkeller K, Ambrosi G, Klemm N, et al.2022. Metabolic balance in colorectal cancer is maintained by optimal Wnt signaling levels[J]. Molecular Systems Biology, 18(8): 10874-10882. [7] Infantino V, Santarsiero A, Convertini P, et al.2021. Cancer cell metabolism in hypoxia: Role of hif-1 as key regulator and therapeutic target[J]. International Journal of Molecular Sciences, 22(11): 5703-5721. [8] Jiang H, Chai Z X, Chen X Y, et al.2024. Yak genome database: A multi-omics analysis platform[J]. BMC Genomics, 25(1): 346-352. [9] Jing L, An Y H, Cai T X, et al.2023. A subpopulation of CD146+ macrophages enhances antitumor immunity by activating the NLRP3 inflammasome[J]. Cellular Molecular Immunology, 20(8): 908-923. [10] Jin R, Gao Q, Yin C, et al.2022. The CD146-HIF-1α axis regulates epithelial cell migration and alveolar maturation in a mouse model of bronchopulmonary dysplasia[J]. Laboratory Investigation, 102(8): 794-804. [11] Khan R, Di G C M, Lee J, et al.2024. The contribution of age-related changes in the gut-brain axis to neurological disorders[J]. Gut Microbes, 16(1): 2302801-23028026. [12] Kowalski K, Mulak A.2019. Brain-gut-microbiota axis in alzheimer's disease[J]. Journal of Neurogastroenterology and Motility, 25(1): 48-60. [13] Kraimi N, Ross T, Pujo J, et al.2024. The gut microbiome in disorders of gut-brain interaction[J]. Gut Microbes, 16(1): 2360233-2360241. [14] Lee S J, Kim H P, Jin Y, et al.2011. Beclin 1 deficiency is associated with increased hypoxia-induced angiogenesis[J]. Autophagy, 7(8): 829-839. [15] Leroyer A S, Blin M G, Bachelier R, et al.2019. CD146 (cluster of differentiation 146)[J]. Arteriosclerosis Thrombosis Vascular Biology, 39(6): 1026-1033. [16] Loh J S, Mak W Q, Tan L K S, et al.2024. Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases[J]. Signal Transduction and Target Therapy, 9(1): 37-45. [17] Luo Y T, Teng X, Zhang L L, et al.2019. CD146-HIF-1α hypoxic reprogramming drives vascular remodeling and pulmonary arterial hypertension[J]. Nature Communications, 10(1): 3551-3568. [18] Manda K, Ueno M, Anzai K.2008. Melatonin mitigates oxidative damage and apoptosis in mouse cerebellum induced by high-LET 56Fe particle irradiation[J]. Journal of Pineal Research, 44(2): 189-196. [19] Madai S, Kilic P, Schmidt R M, et al.2024. Activation of the hypoxia-inducible factor pathway protects against acute ischemic stroke by reprogramming central carbon metabolism[J]. Theranostics, 14(7): 2856-2880. [20] Ma R, Cui Y, Yu S J, et al.2024. Whole transcriptome sequencing revealed the gene regulatory network of hypoxic response in yak Sertoli cells[J]. Scientific Reports, 14(1): 19903-19916. [21] Schneider E, O'Riordan K J, Clarke G, et al.2024. Feeding gut microbes to nourish the brain: Unravelling the diet-microbiota-gut-brain axis[J]. Nature Metabolism, 6(8): 1454-1478 [22] Tsao C C, Baumann J, Huang S F, et al.2021. Pericyte hypoxia-inducible factor-1 (HIF-1) drives blood-brain barrier disruption and impacts acute ischemic stroke outcome[J]. Angiogenesis, 24(4): 823-842. [23] Wang F X, Chen L, Kong D, et al.2024. Canonical Wnt signaling promotes HSC glycolysis and liver fibrosis through an LDH-A/HIF-1α transcriptional complex[J]. Hepatology, 79(3): 606-623. [24] Wang Z Q, Xu Q J, Zhang N W, et al.2020. CD146, from a melanoma cell adhesion molecule to a signaling receptor[J]. Signal Transduction Targeted Therapy, 5(1): 148-160. [25] Wang Z Q, Yan X Y.2013. CD146, a multi-functional molecule beyond adhesion[J]. Cancer Letters, 330(2): 150-162. [26] Wu Z Z, Zang Y Z, Li C Y, et al.2024. CD146, a therapeutic target involved in cell plasticity[J]. Science China Life Sciences, 67(8): 1563-1578. [27] Xie Y, Sun Y, Liu Y D, et al.2023. Targeted delivery of rgd-CD146+CD271+ human umbilical cord mesenchymal stem cell-derived exosomes promotes blood-spinal cord barrier repair after spinal cord injury[J].ACS Nano, 17(18): 18008-18024. [28] Xu W Y, Hua H J, Chiu Y H, et al.2019. CD146 regulates growth factor-induced mTORC2 activity independent of the PI3K and mTORC1 pathways[J]. Cell Reports, 29(5): 1311-1322. [29] Xue B, Wang P, Yu W Z, et al.2022. CD146 as a promising therapeutic target for retinal and choroidal neovascularization diseases[J]. Science China Life Sciences, 65(6): 1157-1170. [30] Zhang L, Yang K, Tan X, et al.2024. Analysis of age-related differences in hypoxia-related factors in yak brain tissue[J]. Folia Morphological (Warsz), 83(2): 341-324. [31] Zhang Q, Cui Y, Yu S J, et al.2022a. Immune cells in the small intestinal mucosa of newborn yaks[J]. Folia Morphological (Warsz), 81(1): 91-100. [32] Zhang Q, Yang K, Pan Y Y, et al.2016. Age-related changes in the morphology and protein expression of the thymus of healthy yaks (Bos grunniens)[J]. American Journal Veterinary Research, 77(6): 567-574. [33] Zhang R H, Chen X G, Chen S W, et al.2022b. Inhibition of CD146 lessens uveal melanoma progression through reducing angiogenesis and vasculogenic mimicry[J]. Cellular Oncology, 45(4): 557-572. [34] Zhang Y, Archie S R, Ghanwatkar Y, et al.2022c. Potential role of astrocyte angiotensin converting enzyme 2 in the neural transmission of COVID-19 and a neuroinflammatory state induced by smoking and vaping[J]. Fluids and Barriers of the CNS, 19(1): 46-48. [35] Zhang Y Y, Zhou M L, Liang Y X, et al.2023. Study of transcriptomic analysis of yak (Bos grunniens) and cattle (Bos taurus) pulmonary artery smooth muscle cells under oxygen concentration gradients and differences in their lung histology and expression of pyruvate dehydrogenase kinase 1-related factors[J]. Animals (Basel), 13(22): 3450-3462. [36] Zhou M L, Wang J, Cao R R, et al.2024. Hypoxia-induced differences in the expression of pyruvate dehydrogenase kinase 1-related factors in the renal tissues and renal interstitial fibroblast-like cells of yak (Bos grunniens)[J]. Animals (Basel), 14(21): 3110-3121. [37] Zhuang J, Jiang T X, Lu D, et al.2010. NADPH oxidase 4 mediates reactive oxygen species induction of CD146 dimerization in VEGF signal transduction[J]. Free Radical Biology Medicine, 49(2): 227-236.
