Cycloxygenase-2 activates EGFR – ERK1/2 pathway via PGE2 mediated ADAM-17 signaling in testosterone-induced benign prostatic hyperplasia

• DOI: 10.22541/au.165728001.12849314/v1
• Publication Date: 2022-07-08T11:33:39Z
• Authors: Mohammed Aboul Fo...; Maha Mohammed; Wafaa Mohamed; Laila Ramadan; Hassan Afify
• Keywords: Male; 0301 basic medicine; MAP Kinase Signaling System; Endocrinology, Diabetes and Metabolism; Prostaglandin E2; Prostatic Hyperplasia; Cyclooxygenase-2 Inhibitors in Inflammation and Cancer; Apoptosis; ADAM17 Protein; Biochemistry; Gene; Dinoprostone; Rats, Sprague-Dawley; 03 medical and health sciences; Endocrinology; Biochemistry, Genetics and Molecular Biology; Health Sciences; Genetics; Animals; Testosterone; Rats, Wistar; Internal medicine; Long-Term Effects of Testosterone on Health; Cancer; Pharmacology; Inflammation; Testosterone (patch); Hyperplasia; CREB; Benign prostatic hyperplasia (BPH); Prostate; Life Sciences; Transforming Growth Factor alpha; Immunohistochemistry; Rats; Cyclooxygenase; 3. Good health; ErbB Receptors; Chemistry; Cyclooxygenase 2; Celecoxib; Enzyme; FOS: Biological sciences; Medicine; Original Article; Transcription factor; Mechanisms of Estrogen Receptor Signaling

Background and Purpose: One of the most bothersome disorders affecting elderly men is benign prostatic hyperplasia (BPH). Prostatic inflammation driving force behind hyperplasia. A pro-inflammatory response in prostate has been linked to a number cytokines growth factors. The current study evaluated association between BPH. Experimental Approach: standard selective COX-2 inhibitor; Celecoxib (CXB) (10 20 mg/kg) was injected i.p. daily into male Wister rats for three weeks. From second week, testosterone (TST) (3 s.c. induce Key Results: In TST-treated rats, there marked increase COX-2, concurrently with an elevation weight index as well. Moreover, TST-induced elucidated by deleterious changes histopathological cytoskeleton. addition, overexpression PGE2 , NF-κB (p65) IL-6 could be attributed induced TST. Additionally, COX-2-derived increased activity ADAM-17 TGF-α TNF-α . Consequently, EGFR –ERK1/2 pathway activated. Collectively, normal balance cell proliferation (Bcl-2 Cyclin D1) apoptosis (Bax ) disrupted. By using CXB, effects were reversed. Conclusion Implications: It can concluded that critical overactivation EGFR–ERK1/2 Concisely, induces ERK1/2 via PGE2–ADAM-17 catalyzed shedding present work augments functional correlation