ABSTRACT:

Growth factor (TGF-β1) belongs to the superfamily (TGF-β) as it has different roles and functions and participates in various physiological, biological, and pathological processes. The protein (TGF-β1) works to regulate cellular processes through pathways in which there is a connection to membrane receptors, which are of two types, I and II. Gene expression (TGF-β1) as well as its receptors can occur in the human placenta. This study aimed to identify some molecular parameters that could be considered accurate diagnostic parameters. Predictive bioinformatics techniques were used to predict whether the change occurring in the amino acid within the protein chain would affect the function of the protein in the future and thus the occurrence of the disease. The disease database, in which mutations were found, will be used and registered in the future. Mutations that occurred in the coding region that changed the amino acid in the protein were identified and tabulated in special tables. After that, the protein’s sequence was obtained, and four predictive bioinformatics algorithms were applied. The results of this study showed that most of the mutations affect the natural protein. The effect may be on the physical and chemical properties, and it may be on the structural stability of the protein. Conclusions The candidate mutations in this study are mutations that can be considered diagnostic molecular indicators of preeclampsia.

REFERENCES :

1) Cheng, J. C., Gao, Y., Chen, J., Meng, Q., & Fang, L. (2023). EGF promotes human trophoblast cell invasion by downregulating CTGF expression via PI3K/AKT signaling. Reproduction, 165(1), 113-122. ‏
2) Szydełko-Gorzkowicz, M., Poniedziałek-Czajkowska, E., Mierzyński, R., Sotowski, M., & Leszczyńska-Gorzelak, B. (2022). The role of kisspeptin in the pathogenesis of pregnancy complications: a narrative review. International Journal of Molecular Sciences, 23(12), 6611.‏
3) Li, H., Peng, H., Hong, W., Wei, Y., Tian, H., Huang, X., … & Wang, K. (2023). Human Placental Endothelial Cell and Trophoblast Heterogeneity and Differentiation Revealed by Single-Cell RNA Sequencing. Cells, 12(1), 87.‏
4) Partalidou, S., Mamopoulos, A., Dimopoulou, D., & Dimitroulas, T. (2023). Pregnancy outcomes in Takayasu arteritis patients: a systematic review and meta-analysis. Scientific Reports, 13(1), 546.‏
5) Harihar, S., & Welch, D. R. (2023). KISS1 metastasis suppressor in tumor dormancy: a potential therapeutic target for metastatic cancers?. Cancer and Metastasis Reviews, 1-14.‏
6) Mills, E. G., Izzi-Engbeaya, C., Abbara, A., Comninos, A. N., & Dhillo, W. S. (2021). Functions of galanin, spexin and kisspeptin in metabolism, mood and behaviour. Nature Reviews Endocrinology, 17(2), 97-113.‏
7) Duarte, J. C. G., Ferreira, J. G. P., & Bittencourt, J. C. (2023). The effect of estrogen and progesterone on melanin-concentrating hormone producing-neurons in brain areas related to reproductive behavior in lactating dams. Journal of Chemical Neuroanatomy, 128, 102208.‏
8) Szydełko-Gorzkowicz, M., Poniedziałek-Czajkowska, E., Mierzyński, R., Sotowski, M., & Leszczyńska-Gorzelak, B. (2022). The role of kisspeptin in the pathogenesis of pregnancy complications: a narrative review. International Journal of Molecular Sciences, 23(12), 6611.‏
9) Zhang, S., Xiao, Y., Wang, Y., Qian, C., Zhang, R., Liu, J., … & Zhang, H. (2023). Role of kisspeptin in decidualization and unexplained recurrent spontaneous abortion via the ERK1/2 signalling pathway. Placenta.‏
10) Fang, L., Yan, Y., Gao, Y., Wu, Z., Wang, Z., Yang, S., … & Sun, Y. P. (2022). TGF-β1 inhibits human trophoblast cell invasion by upregulating kisspeptin expression through ERK1/2 but not SMAD signaling pathway. Reproductive Biology and Endocrinology, 20(1), 22.‏
11) Grassi, D., Marraudino, M., García-Segura, L. M., & Panzica, G. C. (2022). The hypothalamic paraventricular nucleus as a central hub for the estrogenic modulation of neuroendocrine function and behavior. Frontiers in Neuroendocrinology, 65, 100974.‏
12) Cheng, J. C., Gao, Y., Chen, J., Meng, Q., & Fang, L. (2023). EGF promotes human trophoblast cell invasion by downregulating CTGF expression via PI3K/AKT signaling. Reproduction, 165(1), 113-122.‏
13) Gomes, V. C., & Sones, J. L. (2021). From inhibition of trophoblast cell invasion to proapoptosis: what are the potential roles of kisspeptins in preeclampsia?. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 321(1), R41-R48.‏
14) Calthorpe, R. J., Poulter, C., Smyth, A. R., Sharkey, D., Bhatt, J., Jenkins, G., & Tatler, A. L. (2023). Complex roles of TGF-beta signaling pathways in lung development and bronchopulmonary dysplasia. American Journal of Physiology-Lung Cellular and Molecular Physiology.‏
15) Mirzaei, S., Paskeh, M. D. A., Saghari, Y., Zarrabi, A., Hamblin, M. R., Entezari, M., … & Samarghandian, S. (2022). Transforming growth factor-beta (TGF-β) in prostate cancer: A dual function mediator?. International Journal of Biological Macromolecules.‏
16) Liu, S., Baeg, G. H., Yang, Y., Goh, F. G., Bao, H., Wagner, E. J., … & Cai, Y. (2023). The Integrator complex desensitizes cellular response to TGF-β/BMP signaling. Cell Reports, 42(1), 112007.‏
17) Dewidar, B., Meyer, C., Dooley, S., & Meindl-Beinker, N. (2019). TGF-β in hepatic stellate cell activation and liver fibrogenesis—updated 2019. Cells, 8(11), 1419.‏
18) Zhao, X., Sun, D., Zhang, A., Huang, H., Li, Y., & Xu, D. (2023). Candida albicans-induced activation of the TGF-β/Smad pathway and upregulation of IL-6 may contribute to intrauterine adhesion. Scientific Reports, 13(1), 579.‏
19) Tian J, Al-Odaini AA, Wang Y, Korah J, Dai M, Xiao L, et al. KiSS1 gene as a novel mediator of TGFbeta-mediated cell invasion in triple negative breast cancer. Cell Signal. 2018;42:1–10.
20) Haider, S., Lackner, A. I., Dietrich, B., Kunihs, V., Haslinger, P., Meinhardt, G., … & Knöfler, M. (2022). Transforming growth factor-β signaling governs the differentiation program of extravillous trophoblasts in the developing human placenta. Proceedings of the National Academy of Sciences, 119(28), e2120667119.‏
21) Long, Y., Zeng, S., Gao, F., Liu, F., Zhang, Y., Zhou, C., … & Yang, H. (2023). SERPINA5 may promote the development of preeclampsia by disruption of the uPA/uPAR pathway. Translational Research, 251, 14-26.‏
22) Mukherjee, I., Singh, S., Karmakar, A., Kashyap, N., Mridha, A. R., Sharma, J. B., … & Karmakar, S. (2022). New immune horizons in therapeutics and diagnostic approaches to preeclampsia. American Journal of Reproductive Immunology.‏
23) Yi, Y., Cheng, J. C., Klausen, C., & Leung, P. C. (2018). TGF-β1 inhibits human trophoblast cell invasion by upregulating cyclooxygenase-2. Placenta, 68, 44-51.‏
24) Vivekanandam, V., Ellmers, R., Jayaseelan, D., Houlden, H., Männikkö, R., & Hanna, M. G. (2022). In silico versus functional characterization of genetic variants: lessons from muscle channelopathies. Brain.‏
25) Guzzi, A. F., Oliveira, F. S. L., Amaro, M. M. S., Tavares-Filho, P. F., & Gabriel, J. E. (2019). In silico prediction of the functional and structural consequences of the non-synonymous single nucleotide polymorphism A122V in bovine CXC chemokine receptor type 1. Brazilian Journal of Biology, 80, 39-46.‏
26) Yaseen, O. Q., Al-Ani, M. Q., & Majeed, Y. H. (2020). In-Silico prediction of impact on protein function caused by non-synonymous single nucleotide polymorphism in human ATP7B gene associated with Wilson disease. Research Journal of Biotechnology Vol, 15, 3.‏
27) Livesey, B. J., & Marsh, J. A. (2022). Interpreting protein variant effects with computational predictors and deep mutational scanning. Disease Models & Mechanisms, 15(6), dmm049510.‏
28) Livesey, B. J., & Marsh, J. A. (2020). Using deep mutational scanning to benchmark variant effect predictors and identify disease mutations. Molecular systems biology, 16(7), e9380.‏
29) Quan, L., Wu, H., Lyu, Q., & Zhang, Y. (2019). DAMpred: Recognizing Disease-Associated nsSNPs through Bayes-Guided Neural-Network Model Built on Low-Resolution Structure Prediction of Proteins and Protein–Protein Interactions. Journal of molecular biology, 431(13), 2449-2459.‏