Research Article
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Year 2026, Volume: 28 Issue: 1 , 64 - 70 , 25.04.2026
https://doi.org/10.18678/dtfd.1795229
https://izlik.org/JA34AS47CX

Abstract

References

  • Yadav P, Bobrowski A, Ahmad I, Kim JK, Chancy M, Alshammari D, et al. A scoping review on chordee correction in boys with ventral congenital penile curvature and hypospadias. Indian J Urol. 2024;40(1):17-24. doi:10.4103/iju.iju_277_23.
  • Madec FX, Akakpo W, Ferretti L, Carnicelli D, Terrier JÉ, Methorst C, et al. Courbures congénitales du pénis : recommandations du Comité d’andrologie et de médecine sexuelle de l’Association française d’urologie [Congenital penile curvature: guidelines from the Andrology and Sexual Medicine Committee of the French Association of Urology (CAMS-AFU)]. Prog Urol. 2022;32(10):656-63. French. doi:10.1016/j.purol.2022.04.010.
  • Yachia D. Re: an unanswered question in pediatric urology: the post pubertal persistence of prepubertal congenital penile curvature correction by tunical plication. Int Braz J Urol. 2018;44(2):411-2. doi:10.1590/S1677-5538.IBJU.2017.0055.1.
  • Capece M, Cilio S, Morgado A, Capogrosso P, Celentano G, Altieri V, et al. Congenital penile curvature treatments in adults: a systematic review of techniques and outcomes. Int J Impot Res. 2026;38(3):161-75. doi:10.1038/s41443-025-01033-6.
  • Özbilen MH, Sağmak B, Çakıcı MÇ, Ayhan L, Keser F, Kartal SB, et al. Factors affecting the success of corporoplasty based on geometric principles in patients with congenital penile curvature. J Sex Med. 2025;22(8):1475-82. doi:10.1093/jsxmed/qdaf143.
  • Gadelkareem RA, Elgendy MA, Kurkar A, El-Taher AM, Abdelkawi IF. Isolated ventral congenital penile curvature treated by incisionless plication of tunica albuginea in adults: A prospective case series. Curr Urol. 2023;17(3):206-12. doi:10.1097/CU9.0000000000000121.
  • Hartmann S, Ridley AJ, Lutz S. The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol. 2015;6:276. doi:10.3389/fphar.2015.00276.
  • Julian L, Olson MF. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases. 2014;5:e29846. doi:10.4161/sgtp.29846.
  • Lisowska J, Rödel CJ, Manet S, Miroshnikova YA, Boyault C, Planus E, et al. The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. J Cell Sci. 2018;131(15):jcs216093. doi:10.1242/jcs.216093.
  • Sedmera D, Olejnickova V, Sankova B, Kolesova H, Bartos M, Kvasilova A, et al. Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling. Front Cell Dev Biol. 2024;12:1471751. doi:10.3389/fcell.2024.1471751.
  • Kalınlı EM, Akbas E, Yolal Ertural D, Gunes S. Investigation of RhoA, ROCK1, and ROCK2 gene expressions in autism spectrum disorders. Cureus. 2024;16(11):e74810. doi:10.7759/cureus.74810.
  • Cossard A, Stam K, Smets A, Jossin Y. MKL/SRF and Bcl6 mutual transcriptional repression safeguards the fate and positioning of neocortical progenitor cells mediated by RhoA. Sci Adv. 2023;9(46):eadd0676. doi:10.1126/sciadv.add0676.
  • Mitsui Y, Yamabe F, Hori S, Uetani M, Kobayashi H, Nagao K, et al. Molecular mechanisms and risk factors related to the pathogenesis of Peyronie's disease. Int J Mol Sci. 2023;24(12):10133. doi:10.3390/ijms241210133.
  • Jiang HS, Zhu LL, Zhang Z, Chen H, Chen Y, Dai YT. Estradiol attenuates the TGF-β1-induced conversion of primary TAFs into myofibroblasts and inhibits collagen production and myofibroblast contraction by modulating the Smad and Rho/ROCK signaling pathways. Int J Mol Med. 2015;36(3):801-7. doi:10.3892/ijmm.2015.2288.
  • Yang X, Wu J, Cai T, Shan J, Cui Y. Kindlin-2 mediates Peyronie's disease through activation of TGF-β/Smad signaling pathway under the presence of TGF-β1. Cell Signal. 2024;121:111286. doi:10.1016/j.cellsig.2024.111286.
  • Cohen DJ, Reynaldo WV, Borba VB, Theodoro TR, Petri G, Cavalheiro RP, et al. New in vivo model to assess macroscopic, histological, and molecular changes in Peyronie's disease. Andrology. 2022;10(1):154-65. doi:10.1111/andr.13092.
  • Yamamura A, Nayeem MJ, Sato M. The Rho kinase 2 (ROCK2)-specific inhibitor KD025 ameliorates the development of pulmonary arterial hypertension. Biochem Biophys Res Commun. 2021;534:795-801. doi:10.1016/j.bbrc.2020.10.106.
  • Yu L, Zeng F, Fan M, Zhang K, Duan J, Tan Y, et al. PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior. Zool Res. 2024;45(3):535-50. doi:10.24272/j.issn.2095-8137.2024.055.

Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies

Year 2026, Volume: 28 Issue: 1 , 64 - 70 , 25.04.2026
https://doi.org/10.18678/dtfd.1795229
https://izlik.org/JA34AS47CX

Abstract

Aim: To investigate whether RhoA/ROCK pathway genes (RHOA, ROCK1, ROCK2) are differentially expressed in tunica albuginea of patients with congenital penile curvature (CPC) relative to Peyronie's disease (PD) and erectile dysfunction (ED), and to determine whether any differential expression is independent of clinical confounders. Material and Methods: This study enrolled 52 patients across three groups, as CPC (n=15), PD (n=15), and ED requiring penile prosthesis implantation (n=22). Tunica albuginea biopsies were obtained intraoperatively at standardised sites. RHOA, ROCK1, and ROCK2 mRNA levels were quantified by real-time qPCR using the 2-ΔΔCt method, normalised to GAPDH. Confounder adjustment was performed by multivariable linear regression and 1:2 nearestneighbour propensity score matching. Results: ROCK2 mRNA was elevated in CPC compared with PD (fold change, 1.28; 95% CI, 1.12-1.44; p=0.016) and ED (fold change, 1.21; 95% CI, 1.05-1.37; p=0.037). Neither RHOA nor ROCK1 differed significantly across groups. CPC group membership independently predicted higher ROCK2 in multivariable regression (β=0.189; 95% CI, 0.048-0.330; p=0.009) and in propensity score matched groups (mean difference, 0.21; 95% CI, 0.06-0.36; p=0.008). ROCK2 expression correlated positively with curvature severity (r=0.58; p=0.020). Conclusion: Selective ROCK2 upregulation distinguishes CPC from acquired penile conditions and is independent of age, BMI, and comorbidity burden. These findings suggest a developmental molecular mechanism distinct from fibrotic remodelling. Validation in larger multicentre cohorts with protein-level confirmation is required before clinical application.

Ethical Statement

This study was approved by the Mersin University Clinical Research Ethics Committee (14.09.2022, 2022/627).

References

  • Yadav P, Bobrowski A, Ahmad I, Kim JK, Chancy M, Alshammari D, et al. A scoping review on chordee correction in boys with ventral congenital penile curvature and hypospadias. Indian J Urol. 2024;40(1):17-24. doi:10.4103/iju.iju_277_23.
  • Madec FX, Akakpo W, Ferretti L, Carnicelli D, Terrier JÉ, Methorst C, et al. Courbures congénitales du pénis : recommandations du Comité d’andrologie et de médecine sexuelle de l’Association française d’urologie [Congenital penile curvature: guidelines from the Andrology and Sexual Medicine Committee of the French Association of Urology (CAMS-AFU)]. Prog Urol. 2022;32(10):656-63. French. doi:10.1016/j.purol.2022.04.010.
  • Yachia D. Re: an unanswered question in pediatric urology: the post pubertal persistence of prepubertal congenital penile curvature correction by tunical plication. Int Braz J Urol. 2018;44(2):411-2. doi:10.1590/S1677-5538.IBJU.2017.0055.1.
  • Capece M, Cilio S, Morgado A, Capogrosso P, Celentano G, Altieri V, et al. Congenital penile curvature treatments in adults: a systematic review of techniques and outcomes. Int J Impot Res. 2026;38(3):161-75. doi:10.1038/s41443-025-01033-6.
  • Özbilen MH, Sağmak B, Çakıcı MÇ, Ayhan L, Keser F, Kartal SB, et al. Factors affecting the success of corporoplasty based on geometric principles in patients with congenital penile curvature. J Sex Med. 2025;22(8):1475-82. doi:10.1093/jsxmed/qdaf143.
  • Gadelkareem RA, Elgendy MA, Kurkar A, El-Taher AM, Abdelkawi IF. Isolated ventral congenital penile curvature treated by incisionless plication of tunica albuginea in adults: A prospective case series. Curr Urol. 2023;17(3):206-12. doi:10.1097/CU9.0000000000000121.
  • Hartmann S, Ridley AJ, Lutz S. The function of rho-associated kinases ROCK1 and ROCK2 in the pathogenesis of cardiovascular disease. Front Pharmacol. 2015;6:276. doi:10.3389/fphar.2015.00276.
  • Julian L, Olson MF. Rho-associated coiled-coil containing kinases (ROCK): structure, regulation, and functions. Small GTPases. 2014;5:e29846. doi:10.4161/sgtp.29846.
  • Lisowska J, Rödel CJ, Manet S, Miroshnikova YA, Boyault C, Planus E, et al. The CCM1-CCM2 complex controls complementary functions of ROCK1 and ROCK2 that are required for endothelial integrity. J Cell Sci. 2018;131(15):jcs216093. doi:10.1242/jcs.216093.
  • Sedmera D, Olejnickova V, Sankova B, Kolesova H, Bartos M, Kvasilova A, et al. Morphological, electrophysiological, and molecular alterations in foetal noncompacted cardiomyopathy induced by disruption of ROCK signalling. Front Cell Dev Biol. 2024;12:1471751. doi:10.3389/fcell.2024.1471751.
  • Kalınlı EM, Akbas E, Yolal Ertural D, Gunes S. Investigation of RhoA, ROCK1, and ROCK2 gene expressions in autism spectrum disorders. Cureus. 2024;16(11):e74810. doi:10.7759/cureus.74810.
  • Cossard A, Stam K, Smets A, Jossin Y. MKL/SRF and Bcl6 mutual transcriptional repression safeguards the fate and positioning of neocortical progenitor cells mediated by RhoA. Sci Adv. 2023;9(46):eadd0676. doi:10.1126/sciadv.add0676.
  • Mitsui Y, Yamabe F, Hori S, Uetani M, Kobayashi H, Nagao K, et al. Molecular mechanisms and risk factors related to the pathogenesis of Peyronie's disease. Int J Mol Sci. 2023;24(12):10133. doi:10.3390/ijms241210133.
  • Jiang HS, Zhu LL, Zhang Z, Chen H, Chen Y, Dai YT. Estradiol attenuates the TGF-β1-induced conversion of primary TAFs into myofibroblasts and inhibits collagen production and myofibroblast contraction by modulating the Smad and Rho/ROCK signaling pathways. Int J Mol Med. 2015;36(3):801-7. doi:10.3892/ijmm.2015.2288.
  • Yang X, Wu J, Cai T, Shan J, Cui Y. Kindlin-2 mediates Peyronie's disease through activation of TGF-β/Smad signaling pathway under the presence of TGF-β1. Cell Signal. 2024;121:111286. doi:10.1016/j.cellsig.2024.111286.
  • Cohen DJ, Reynaldo WV, Borba VB, Theodoro TR, Petri G, Cavalheiro RP, et al. New in vivo model to assess macroscopic, histological, and molecular changes in Peyronie's disease. Andrology. 2022;10(1):154-65. doi:10.1111/andr.13092.
  • Yamamura A, Nayeem MJ, Sato M. The Rho kinase 2 (ROCK2)-specific inhibitor KD025 ameliorates the development of pulmonary arterial hypertension. Biochem Biophys Res Commun. 2021;534:795-801. doi:10.1016/j.bbrc.2020.10.106.
  • Yu L, Zeng F, Fan M, Zhang K, Duan J, Tan Y, et al. PCDH17 restricts dendritic spine morphogenesis by regulating ROCK2-dependent control of the actin cytoskeleton, modulating emotional behavior. Zool Res. 2024;45(3):535-50. doi:10.24272/j.issn.2095-8137.2024.055.
There are 18 citations in total.

Details

Primary Language English
Subjects Urology
Journal Section Research Article
Authors

Mustafa Sesli 0000-0001-5200-698X

Selahittin Çayan 0000-0003-4784-2208

Ebru Derici Eker 0000-0002-7094-7625

Mert Başaranoğlu 0000-0002-9873-4920

Kansu Büyükafşar 0000-0003-4117-6013

Erdem Akbay 0000-0001-7669-414X

Submission Date October 1, 2025
Acceptance Date April 13, 2026
Publication Date April 25, 2026
DOI https://doi.org/10.18678/dtfd.1795229
IZ https://izlik.org/JA34AS47CX
Published in Issue Year 2026 Volume: 28 Issue: 1

Cite

APA Sesli, M., Çayan, S., Derici Eker, E., Başaranoğlu, M., Büyükafşar, K., & Akbay, E. (2026). Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies. Duzce Medical Journal, 28(1), 64-70. https://doi.org/10.18678/dtfd.1795229
AMA 1.Sesli M, Çayan S, Derici Eker E, Başaranoğlu M, Büyükafşar K, Akbay E. Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies. Duzce Med J. 2026;28(1):64-70. doi:10.18678/dtfd.1795229
Chicago Sesli, Mustafa, Selahittin Çayan, Ebru Derici Eker, Mert Başaranoğlu, Kansu Büyükafşar, and Erdem Akbay. 2026. “Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies”. Duzce Medical Journal 28 (1): 64-70. https://doi.org/10.18678/dtfd.1795229.
EndNote Sesli M, Çayan S, Derici Eker E, Başaranoğlu M, Büyükafşar K, Akbay E (April 1, 2026) Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies. Duzce Medical Journal 28 1 64–70.
IEEE [1]M. Sesli, S. Çayan, E. Derici Eker, M. Başaranoğlu, K. Büyükafşar, and E. Akbay, “Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies”, Duzce Med J, vol. 28, no. 1, pp. 64–70, Apr. 2026, doi: 10.18678/dtfd.1795229.
ISNAD Sesli, Mustafa - Çayan, Selahittin - Derici Eker, Ebru - Başaranoğlu, Mert - Büyükafşar, Kansu - Akbay, Erdem. “Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies”. Duzce Medical Journal 28/1 (April 1, 2026): 64-70. https://doi.org/10.18678/dtfd.1795229.
JAMA 1.Sesli M, Çayan S, Derici Eker E, Başaranoğlu M, Büyükafşar K, Akbay E. Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies. Duzce Med J. 2026;28:64–70.
MLA Sesli, Mustafa, et al. “Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies”. Duzce Medical Journal, vol. 28, no. 1, Apr. 2026, pp. 64-70, doi:10.18678/dtfd.1795229.
Vancouver 1.Mustafa Sesli, Selahittin Çayan, Ebru Derici Eker, Mert Başaranoğlu, Kansu Büyükafşar, Erdem Akbay. Selective ROCK2 Upregulation in Congenital Penile Curvature: A Molecular Signature Distinguishing Developmental from Acquired Penile Pathologies. Duzce Med J. 2026 Apr. 1;28(1):64-70. doi:10.18678/dtfd.1795229