The Role of Clusterin (CLU) in the Pathogenesis of Benign Prostatic Hyperplasia: Mechanisms and Potential as a Biomarker: Peran Clusterin (CLU) dalam Patogenesis Hiperplasia Prostat Jinak: Mekanisme dan Potensi sebagai Biomarker

Muhammad Alfi Reza; Muhammad Sidharta Krisna; Fathannia Rizky Diennillah; Jihan Asma Putri; Andy Yulianto

doi:10.52103/jahr.v5i1.2036

Authors

Muhammad Alfi Reza Mallawa Public Health Center, Maros, South Sulawesi, Indonesia
Muhammad Sidharta Krisna Department of Surgery, Faculty of Medicine, Mega Buana University, Palopo, South Sulawesi, Indonesia
Fathannia Rizky Diennillah Primary Clinic UNHAS Baraya, Makassar, South Sulawesi, Indonesia
Jihan Asma Putri Vale Indonesia Main Clinic Enggano, Sorowako, East Luwu, South Sulawesi, Indonesia
Andy Yulianto Pattopakang Publich Health Center, Takalar, South Sulawesi, Indonesia

DOI:

https://doi.org/10.52103/jahr.v5i1.2036

Keywords:

Apoptosis, Benign Prostatic Hyperplasia, Biomarker, Clusterin

Abstract

ABSTRACT

Background: Benign Prostatic Hyperplasia (BPH) is a common urological condition characterized by excessive proliferation of prostate epithelial and stromal cells, leading to lower urinary tract symptoms. Clusterin (CLU), a multifunctional glycoprotein, has been implicated in various cellular processes, including apoptosis regulation, inflammation, and autophagy. However, its exact role in BPH pathogenesis remains unclear.

Objective: This study aims to analyze the role of CLU in the molecular mechanisms underlying BPH and evaluate its potential as a biomarker for disease progression.

Method: A comprehensive analysis of recent literature was conducted to examine CLU expression in BPH tissues and its interactions with inflammatory pathways, hormonal regulation, and cellular homeostasis mechanisms such as apoptosis and autophagy. The study also reviewed CLU’s involvement in epithelial-stromal interactions and its correlation with disease severity.

Results: Increased CLU expression in hyperplastic prostate tissues is associated with chronic inflammation, contributing to aberrant cell proliferation and apoptosis resistance. CLU interacts with inflammatory markers such as TNF-α and IL-6, promoting a microenvironment conducive to disease progression. Additionally, CLU is involved in autophagy dysregulation, which may further sustain cellular survival and resistance to apoptosis. Evidence suggests that hormonal factors, particularly androgens and estrogens, regulate CLU expression, linking it to prostate tissue remodeling. These findings highlight CLU as a potential biomarker for assessing BPH severity and progression.

Conclusion: CLU plays a critical role in BPH pathogenesis by modulating inflammatory responses, apoptosis, and cellular homeostasis. Its increased expression in hyperplastic prostate tissues suggests that it may serve as a novel biomarker for disease progression. However, further studies are needed to validate its clinical applicability and explore targeted therapies aimed at CLU modulation to improve BPH management.

References

Roehrborn CG. Pathophysiology of benign prostatic hyperplasia. Int J Urol. 2016;23(1):3-10.

Chughtai B, Forde JC, Thomas DD, et al. Benign prostatic hyperplasia. Nat Rev Dis Primers. 2016;2:16031.

Choi SY, Bertram S, Glowacka I, Park YW, Pöhlmann S. The impact of clusterin expression on prostate disease progression. Mol Cell Endocrinol. 2017;450:77-84.

Matsumoto K, Shigehara K, Konaka H, Kadono Y, Iwamoto Y, Iijima M, et al. Clusterin as a novel biomarker for assessing the severity of benign prostatic hyperplasia. Int J Urol. 2018;25(8):718-25.

Nicholson TM, Ricke WA. Androgens and estrogens in benign prostatic hyperplasia: past, present and future. Differentiation. 2020;111:63-70.

Wang R, Lin S, Song Y, et al. Proteomic analysis of stromal and epithelial components in benign prostatic hyperplasia reveals potential therapeutic targets. Prostate. 2019;79(9):974-86.

Wang Y, Hayward SW, Cao M. Identification of molecular subtypes in benign prostatic hyperplasia via transcriptome analysis. Am J Pathol. 2021;191(5):868-81.

Patel R, Singh H. Radiotherapy and urinary tract complications: a urological perspective. World J Urol. 2023;41(5):1187-1201.

Roehrborn CG. Benign prostatic hyperplasia: an overview. Rev Urol. 2015;17(1):S3-S14.

Zhang X, Zeng S, Zhang Y, et al. The role of Clusterin in prostate diseases: potential implications in BPH progression. J Urol Res. 2023;45(2):112-124.

Kim JH, Song PH, Ahn HK, et al. Role of clusterin in chronic inflammation of benign prostatic hyperplasia. Urol J. 2021;18(4):321-8.

Tanaka H, Matsui T, Arai Y, et al. Clusterin-mediated regulation of autophagy in benign prostatic hyperplasia. J Cell Biochem. 2020;121(2):1573-82.

Singh P, Wong YY, Tan HT, et al. Clusterin as a novel therapeutic target in prostate disease: A proteomic insight. J Proteome Res. 2019;18(6):2415-26.

Lee S, Kim SJ, Lee Y, et al. The association between clusterin expression and prostatic inflammation in benign prostatic hyperplasia. BJU Int. 2022;129(3):372-81.

Yadav S, Dey P, Ashok A, et al. Role of molecular chaperones in the pathophysiology of benign prostatic hyperplasia. Cell Stress Chaperones. 2018;23(4):567-78.