Effect of Probiotic on the Pax2 Gene Expression during Kidney Development in Mice Embryos
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Background & aim: At several stages of kidney and urinary tract development, Pax2 and Pax8 have become important participants in the urogenital system. Therefore, the aim of this work was to evaluate the effect of probiotic on the pax2 gene expression during kidney development in mice embryos.
Materials & methods: 30 experimental animals (Swiss mice) were utilized, three month-aged and weight ranged between 16-19gm at period April 2025. An acidophilus plus capsule (Solgar, USA) contains lactobacilli culture that injected (intraperitoneal) as two doses: 9*106/0.1 ml CFU and 18*106/0.2 ml CFU during pregnancy and then the fetal kidneys of these two group compare with control in terms of histology and molecular aspect.
Results: Microscopic examination of fetal kidneys in the probiotic 9*106/0.1 ml group showed normal structures. However, 9*106/0.1 ml group demonstrated greater development in the structure of the nephron compared to the control group. The number of glomeruli was greater and more rapidly developed, and the differentiation of the convoluted tubules was faster than in the control group. Furthermore, the capsule surrounding the kidney was better developed. Similarly, in the probiotic 18*106/0.1 ml group, the development of the nephrons was more pronounced than in the control group, and the differentiation of the convoluted tubules and the capsule surrounding the kidney was more distinct and clear. on the other hand, the finding showed that gene expression in studied groups, the mean of folding changes in control group was 0.9325. in 9*106/0.1 ml probiotic group folding changes was 0.9667. in 18*106/0.1 ml probiotic group folding changes was 1.021. The results showed non-significant (P=0.001) changes in gene expression between studied groups.
Conclusions: its concluded that the use of probiotics improves kidney development in fetuses, as the nephrons and urinary convoluted tubules were more developed and differentiated compared to the control group and improved expression of the Pax2 gene in fetal kidneys.
1. Sharma R., Oraly S. F.., Maxime B. Pax genes in renal development, disease and regeneration. Seminars in Cell and Developmental Biology, 2015; 44: 1-7.
2. Muntean C., Camelia C., Balazs B., Claudia B. PAX2 Gene Mutation in Pediatric Renal Disorders—A Narrative Review. Int. J. Mol. Sci. 2023; 24(16), 12737.
3. Harshman, L.A.; Brophy, P.D. PAX2 in human kidney malformations and disease. Pediatr. Nephrol. 2012; 27, 1265–1275.
4. Fletcher, J.; Hu, M.; Berman, Y.; Collins, F.; Grigg, J.; McIver, M.; Ju, H.; Alexander, S.I. Multicystic Dysplastic Kidney and Variable Phenotype in a Family with a Novel Deletion Mutation of PAX2. J. Am. Soc. Nephrol. 2005; 16: 2754–2761.
5. Patel, S.R.; Ranghini, E.; Dressler, G.R. Mechanisms of gene activation and repression by Pax proteins in the developing kidney. Pediatr. Nephrol. 2013; 29: 589–595.
6. Valcheva R., Dieleman L.A. Prebiotics: definition and protective mechanisms, Best Pract. Res. Clin. Gastroenterol. 2016; 30: 27–37.
7. Jiang Y., Li L., Sun H., Shan Y., Liu Y., Liang L., Qu B., Man C., Induction of cytokines via NF-κB and p38 MAP kinase signalling pathways associated with the immunomodulation by Lactobacillus plantarum NDC 75017 in vitro and in vivo, J.Funct. Foods. 2016; 20: 215–221.
8. Ghosh A.R. Probiotics in the Rescue of Gut Inflammation, Therapeutic, Probiotic, and Unconventional Foods, Elsevier, 2018: 101–116
9. van Baarlen P., Troost F., van der Meer C., Hooiveld G., Boekschoten M., Brummer R.J., Kleerebezem M. Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular path-ways, Proc. Natl. Acad. Sci. 2011; 108: 4562–4569.
10. van Baarlen P., Troost F., van der Meer C., Hooiveld G., Boekschoten M., Brummer R.J., Kleerebezem M. Differential NF- B pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance, Proc. Natl. Acad. Sci. 2009; 106: 2371–2376.
11. Plaza-Diaz J., Gomez-Llorente C., Fontana L., Gil A. Modulation of immunity and inflammatory gene expression in the gut, in inflammatory diseases of the gut and in the liver by probiotics. World J Gastroenterol., 2014; 20(42): 15632-15649.
12. Fontana L., Bermudez-Brito M., Plaza-Diaz J., Muñoz-Quezada S., Gil A. Sources, isolation, characterisation and evaluation of probiotics. Br J Nutr., 2013; 109: S35-S50.
13. Bermudez-Brito M., Plaza-Díaz J., Muñoz-Quezada S., Gómez-Llorente C., Gil A. Probiotic mechanisms of action. Ann Nutr Metab., 2012; 61: 160-174.
14. Goyal N., Tiwari R.P., Shukla G. Lactobacillus rhamnosus GG as an effective probiotic for murine giardiasis. Inter Perspect Infect Dis. 2011;4:8.
15. Coelho M.D., Coelho F.A., Mancilha I.M. Probiotic Therapy: A promising strategy for the control of canine hookworm. J Parasitol Res. 2013;6:1-8.
16. Ahmed K.O., Saleh A.H. Effects of Estrogen in Treating Myocardial Damages Caused by Ischemia in Adult Female Rats. International Journal of Drug Delivery Technology, 2021; 11(4): 1474–1477.
17. Saleh A.H., Aldulaimi L.H., Ahmed N.M. Potential of nanoemulsion of spiramycin in alleviating histological and embryonic changes in Swiss albino mice infected with congenital toxoplasmosis. Journal of Applied and Natural Science, 2024; 16(4): 1842–1848.
18. Imgrund M., Elisabeth G., Hermann-Josef. G., Matthias K., Lawrence H., Detlef S., Uwe W. R. Re-expression of the developmental gene Pax-2 during experimental acute tubular necrosis in mice. Kidney International, 1999; 56: 1423–1431
19. Flurkey K., Currer J.M., Harrison D.E. Chapter 20—Mouse Models in Aging Research. In The Mouse in Biomedical Research, 2nd ed.; Fox J.G., Davisson M.T., Quimby F.W., Barthold S.W., Newcomer C.E., Smith A.L., Eds.; Academic Press: Burlington, ON, Canada, 2007; 637–672.
20. Saadatzadeh A., Fazeli M.R., Jamalifar H., Dinarvand R. Probiotic properties of lyophilized cell-free extract of Lactobacillus casei. Jundishapur J. Nat. Pharm. Prod. 2013; 8:131–137.
21. Lu Y., Liu Y., Yang C. Evaluating In Vitro DNA damage using Comet assay. J. Vis. Exp. 2017; 128:e56450.
22. Sanders, M.E. Considerations for use of probiotic bacteria to modulate human health. J. Nutr. 2000; 130: 384S–390S.
23. Hill C., Guarner, F., Reid G., Gibson G.R., Merenstein D.J., Pot B., Morelli L., Canani R.B., Flint H.J., Salminen S. Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat. Rev. Gastroenterol. Hepatol. 2014; 11: 506–514.
24. Ranganathan N., Ranganathan P., Friedman E.A., Joseph A., Delano B., Goldfarb D.S., Tam P., Rao A.V., Anteyi E., Musso C.G. Pilot study of probiotic dietary supplementation for promoting healthy kidney function in patients with chronic kidney disease. Adv. Ther. 2010; 27: 634–647.
25. Wang I.K., Yen T.H., Hsieh P.S., Ho H.H., Kuo Y.W., Huang Y.Y., Kuo, Y.L., Li C.Y., Lin H.C., Wang J.Y. Effect of a Probiotic Combination in an Experimental Mouse Model and Clinical Patients With Chronic Kidney Disease: A Pilot Study. Front. Nutr., 2021; 8: 661794.
26. Bouchard, M., Schleiffer, A., Eisenhaber, F., and Busslinger, M. 2003. Evolution and function of Pax genes. In Encyclopedia of the Human Genome (ed. D. Cooper). Genes Dev. 2002; 16(22):2958–2970.
27. Dressler G.R., Wilkinson J.E., Rothenpieler U.W., Patterson L.T., Williams-Simons L., Westphal H. Deregulation of Pax-2expression in transgenic mice generates severe kidney abnormalities. Nature, 1993; 362: 65-67.
28. Dressler G., Adrian W. Pax2 in development and renal disease. The International Journal of Developmental Biology, 1999; 43(5): 463-468.
29. Herzlinger D., Qiao J., Cohen D., Ramakrishna N., Brown A.M. Induction of kidney epithelial morphogenesis by cell expressing Wnt-1 .Dev. Biol. 1994; 166: 815-818.
30. Kispert A., Vainio S., Mcmahon A.P. Wnt-4 is a mesenchymalsignal for epithelial transformation of metanephric mesenchyme in the developingkidney. Development, 1998; 125: 4225-4234.
31. Bai S. P., WU A., Ding X. M., Lei Y., Bai J., Zhang K. Y., Chio, J. S. Effects of probioticsupplemented diets on growth performance and intestinal immune characteristics of broiler chickens. J. Poultry Science, 2013; 92: 663–667.
32. Mandana S., Mohammad H. M., Seyed N. M., Maryam, T. E. Effects of probiotic lactic acid bacteria on growth performance, carcass characteristics, hematological indices, humoral immunity, and IGF-I gene expression in broiler chicken. J. Tropical Animal Health and Production, 2019; 51; 2279–2286.
33. Kambiz F., Jafar. F., Hossein M., Kumarss A. Dietary Supplementation of Potential Probiotics Bacillus subtilis, Bacillus licheniformis, and Saccharomyces cerevisiae and Symbiotic Improves Growth Performance and Immune Responses by Modulation in Intestinal System in Broiler Chicks Challenged with Salmonella typhimurium. J. Probiotics and Antimicrobial Proteins, 2021; 13: 1081– 1092.
