Shalini Sharma

Introduction: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a single gene disorder, of the PKD1 gene, affecting over 12 million people today.¹ It is characterized by large noncancerous cysts on the patient’s kidneys associated with renal tubular dysfunction, hypertension, renal pain, increased renin production, as well as other symptoms.¹ Methods: Multiple animal studies show promise in influencing the PKD1 promoter region by the Beta-Catenin pathway.² PKD1 was mapped and after some confirmatory testing with co-transfection of HeLa cells and Beta-catenin.² Different segments within the PKD1 were deleted in order to test induction by Beta-catenin.² Specific focus was placed on the TBE1 segment within the PKD1.² Immunofluorescent was used to detect increased expression of PKD1.³ Other sources collected samples of renal tissue and urinary samples from patients affected by ADPKD and not affected patients.³ The glomerular filtration rate, gross clinical pathology, and T cell levels were quantified by flow cytometry.³ Immunofluorescent tagging was used to detect CD3+ T cells and CD68+ T cells.³ Lastly sources tested induction of T cell maturation with co-transfection with Beta-catenin. The results were quantified with flow cytometry.⁴ Results: Flow cytometry data showed increased activity in PKD1 after cells were transfected with beta catenin.³ Examination of PKD1 with deleted segments in the promoter region showed no induced after being transfected with beta catenin.³ Flow cytometry quantifying the amount of CD3+ and CD4+ T cells revealed a significant increase within the tissue and renal samples taken from PKD patients in comparison to non-affected PKD patients.⁴ Immunofluorescent tagging also showed a significant increase in immunofluorescence in samples collected from PKD affected patients.⁴ Flow cytometry quantification of T cells induced by beta catenin showed a 7.8% increase in induction after transfection with beta catenin.⁴ Examination and flow cytometry of mice deficient in TCF1, the specific region within T cell maturation induced by beta catenin, showed a 50% decrease in CD4+ T cell maturation.⁴ Conclusion: Current animal studies have confirmed that beta catenin plays an inductive role in a promoter region in PKD1 and maturity of CD4+ T helper cells that play a role in the pathogenesis in Polycystic Kidney Disease.^2,3,4 Due to the large range of symptoms affecting patients with PKD, future work should be aimed to study the role of beta catenin suppression in PKD disease prognosis and perform a longitudinal study of PKD patients before the disease progresses to renal failure in need of a renal transplant.⁵

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2. Rodova M, Islam MR, Maser RL, Calvet JP. The polycystic kidney disease-1 promoter is a target of the beta-catenin/T-cell factor pathway. J Biol Chem. 2002;277(33):29577-  doi:10.1074/jbc.M203570200
3. Zimmerman KA, Gonzalez NM, Chumley P, et al. Urinary T cells correlate with rate of renal function loss in autosomal dominant polycystic kidney disease. Physiol Rep. 2019;7(1):e13951. doi:10.14814/phy2.13951
4. Huang Z, Xie H, Ioannidis V, et al. Transcriptional regulation of CD4 gene expression by T cell factor-1/beta-catenin pathway. J Immunol. 2006;176(8):4880-4887. doi:10.4049/jimmunol.176.8.4880
5. Suwabe T, Shukoor S, Chamberlain AM, et al. Epidemiology of Autosomal Dominant Polycystic Kidney Disease in Olmsted County. Clin J Am Soc Nephrol. 2020;15(1):69-79.  doi:10.2215/CJN.05900519