سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Liu, Qian, Li, Xiaodong, Zhu, Jingzhen, Sun, Bishao, Li, Shadan. (1402). TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels. , 26(6), 701-707. doi: 10.22038/ijbms.2023.68528.14943
Qian Liu; Xiaodong Li; Jingzhen Zhu; Bishao Sun; Shadan Li. "TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels". , 26, 6, 1402, 701-707. doi: 10.22038/ijbms.2023.68528.14943
Liu, Qian, Li, Xiaodong, Zhu, Jingzhen, Sun, Bishao, Li, Shadan. (1402). 'TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels', , 26(6), pp. 701-707. doi: 10.22038/ijbms.2023.68528.14943
Liu, Qian, Li, Xiaodong, Zhu, Jingzhen, Sun, Bishao, Li, Shadan. TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels. , 1402; 26(6): 701-707. doi: 10.22038/ijbms.2023.68528.14943

TrkA inhibition alleviates bladder overactivity in cyclophosphamide-induced cystitis by targeting hyperpolarization-activated cyclic nucleotide-gated channels

Iranian Journal of Basic Medical Sciences
مقاله 12، دوره 26، شماره 6، شهریور 2023، صفحه 701-707    اصل مقاله (603.12 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2023.68528.14943
نویسندگان
Qian Liu1، 2؛ Xiaodong Li2، 3؛ Jingzhen Zhu4؛ Bishao Sun* 4؛ Shadan Li* 2
1Clinical Medicine Postdoctoral Research Station, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
2Department of Urology, The General Hospital of Western Theater Command, Chengdu, China
3Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
4Department of Urology, Second Affiliated Hospital, Army Medical University, Chongqing, China
چکیده
Objective(s): To investigate the potential of Tropomyosin receptor kinase A (TrkA) for the treatment of interstitial cystitis/ bladder pain syndrome (IC/BPS).
Materials and Methods: Sixty-four female rats were randomly assigned to the control and cyclophosphamide (CYP) groups. Quantitative reverse transcription polymerase chain reaction was utilized to detect the mRNA level of TrkA. Western blot analysis was used to measure the protein levels of TNF-α, IL-6, and TrkA. Immunostaining was used to detect the expression of TrkA in bladder sections. Contractility studies and urodynamic measurements were utilized to test the spontaneous contractions of detrusor muscle strips and the global bladder activity, respectively.
Results: Rat models of chronic cystitis were successfully established. The mRNA and protein levels of TrkA were significantly increased in the bladders of CYP-treated rats. Also, results of immunohistochemical staining and immunofluorescence staining showed that increased TrkA expression in the CYP group was mainly observed in the urothelium layer and bladder interstitial Cajal-like cells (ICC-LCs) but not in the detrusor smooth muscle cells. The specific inhibitor of TrkA, GW441756 (10 μM), significantly suppressed the robust spontaneous contractions of detrusor muscle strips in the CYP group and alleviated the overall bladder overactivity of CYP-treated rats. However, the inhibitory effects of GW441756 (10 μM) on the spontaneous contractions of detrusor muscle strips and the overall bladder activity were eliminated after pretreatments with the specific blocker of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, ZD7288 (50 μM).
Conclusion: Our results suggested that increased TrkA expression during chronic cystitis promotes the development of bladder overactivity by targeting the HCN channels.
کلیدواژه‌ها
Cyclophosphamide؛ Cystitis؛ Hyperpolarization-activated-cyclic nucleotide-gated channels؛ Tropomyosin receptor-kinase A؛ Urinary bladder
مراجع
1. Lin Z, Hu H, Liu B, Chen Y, Tao Y, Zhou X, et al. Biomaterial-assisted drug delivery for interstitial cystitis/bladder pain syndrome treatment. J Mater Chem B 2021; 9:23-34.
2. Li J, Yi X, Ai J. Broaden horizons: The advancement of interstitial cystitis/bladder pain syndrome. Int J Mol Sci 2022; 23:14594-14616.
3. Chuang YC, Chermansky C, Kashyap M, Tyagi P. Investigational drugs for bladder pain syndrome (BPS) / interstitial cystitis (IC). Expert Opin Investig Drugs 2016; 25:521-529.
4. Ko KJ, Lim J, Yu J, Kang D, Cho J, Lee KS. The impact of Hunner lesion-type interstitial cystitis/bladder pain syndrome on health-related quality of life and the effects of transurethral ablation. Qual Life Res 2022; 31:3221-3228.
5. Kanter G, Volpe KA, Dunivan GC, Cichowski SB, Jeppson PC, Rogers RG, et al. Important role of physicians in addressing psychological aspects of interstitial cystitis/bladder pain syndrome (IC/BPS): A qualitative analysis. Int Urogynecol J 2017; 28:249-256.
6. Meng E, Hsu YC, Chuang YC. Advances in intravesical therapy for bladder pain syndrome (BPS)/interstitial cystitis (IC). Low Urin Tract Symptoms 2018; 10:3-11.
7. Rocco ML, Soligo M, Manni L, Aloe L. Nerve growth factor: Early studies and recent clinical trials. Curr Neuropharmacol 2018; 16:1455-1465.
8. Masuoka T, Yamashita Y, Yoshida J, Nakano K, Tawa M, Nishio M, et al. Sensitization of glutamate receptor-mediated pain behaviour via nerve growth factor-dependent phosphorylation of transient receptor potential V1 under inflammatory conditions. Br J Pharmacol 2020; 177:4223-4241.
9. Hirose M, Kuroda Y, Murata E. NGF/TrkA signaling as a therapeutic target for pain. Pain Pract 2016; 16:175-182.
10. Canu N, Amadoro G, Triaca V, Latina V, Sposato V, Corsetti V, et al. The intersection of NGF/TrkA signaling and amyloid precursor protein processing in alzheimer’s disease neuropathology. Int J Mol Sci 2017; 18:1319-1335.
11. Lin C, Ren Z, Yang X, Yang R, Chen Y, Liu Z, et al. Nerve growth factor (NGF)-TrkA axis in head and neck squamous cell carcinoma triggers EMT and confers resistance to the EGFR inhibitor erlotinib. Cancer Lett 2020; 472:81-96.
12. Ochodnicky P, Cruz CD, Yoshimura N, Cruz F. Neurotrophins as regulators of urinary bladder function. Nat Rev Urol 2012; 9:628-637.
13. Antunes-Lopes T, Cruz F. Urinary biomarkers in overactive bladder: Revisiting the evidence in 2019. Eur Urol Focus 2019; 5:329-336.
14. Jiang YH, Jhang JF, Hsu YH, Ho HC, Wu YH, Kuo HC. Urine biomarkers in ESSIC type 2 interstitial cystitis/bladder pain syndrome and overactive bladder with developing a novel diagnostic algorithm. Sci Rep 2021; 11:914-922.
15. Evans RJ, Moldwin RM, Cossons N, Darekar A, Mills IW, Scholfield D. Proof of concept trial of tanezumab for the treatment of symptoms associated with interstitial cystitis. J Urol 2011; 185:1716-1721.
16. Girard BM, Malley S, May V, Vizzard MA. Effects of CYP-induced cystitis on growth factors and associated receptor expression in micturition pathways in mice with chronic overexpression of ngf in urothelium. J Mol Neurosci 2016; 59:531-543.
17. Murray E, Malley SE, Qiao LY, Hu VY, Vizzard MA. Cyclophosphamide induced cystitis alters neurotrophin and receptor tyrosine kinase expression in pelvic ganglia and bladder. J Urol 2004; 172:2434-2439.
18. He C, Chen F, Li B, Hu Z. Neurophysiology of HCN channels: From cellular functions to multiple regulations. Prog Neurobiol 2014; 112:1-23.
19. Lee CH, MacKinnon R. Structures of the human HCN1 hyperpolarization-activated channel. Cell 2017; 168:111-120.
20. Dong X, Song Q, Zhu J, Zhao J, Liu Q, Zhang T, et al. Interaction of caveolin-3 and HCN is involved in the pathogenesis of diabetic cystopathy. Sci Rep 2016; 6:24844-24857.
21. Liu Q, Long Z, Dong X, Zhang T, Zhao J, Sun B, et al. Cyclophosphamide-induced HCN1 channel upregulation in interstitial Cajal-like cells leads to bladder hyperactivity in mice. Exp Mol Med 2017; 49:e319-331.
22. Ko KW, Rasband MN, Meseguer V, Kramer RH, Golding NL. Serotonin modulates spike probability in the axon initial segment through HCN channels. Nat Neurosci 2016; 19:826-834.
23. Maroso M, Szabo GG, Kim HK, Alexander A, Bui AD, Lee SH, et al. Cannabinoid control of learning and memory through HCN channels. Neuron 2016; 89:1059-1073.
24. Wu C, Dong X, Liu Q, Zhu J, Zhang T, Wang Q, et al. EP3 activation facilitates bladder excitability via HCN channels on ICCs. Biochem Biophys Res Commun 2017; 485:535-541.
25. Tooke K, Girard B, Vizzard MA. Functional effects of blocking VEGF/VEGFR2 signaling in the rat urinary bladder in acute and chronic CYP-induced cystitis. Am J Physiol Renal Physiol 2019; 317:F43- F51.
26. Brandolini L, Aramini A, Bianchini G, Ruocco A, Bertini R, Novelli R, et al. Inflammation-independent antinociceptive effects of DF2755A, a CXCR1/2 selective inhibitor: A new potential therapeutic treatment for peripheral neuropathy associated to non-ulcerative interstitial cystitis/bladder pain syndrome. Front Pharmacol 2022; 13:854238-854277.
27. Wang R, Hong M, Huang J, Zhou N, Zhang Y, Xu S, et al. Low-dose cyclophosphamide induces nerve injury and functional overactivity in the urinary bladder of rats. Front Neurosci 2021; 15:715492-715501.
28. Birder L, Andersson KE. Animal modelling of interstitial cystitis/bladder pain syndrome. Int Neurourol J 2018; 22:S3-9.
29. Augé C, Gamé X, Vergnolle N, Lluel P, Chabot S. Characterization and validation of a chronic model of cyclophosphamide-induced interstitial cystitis/bladder pain syndrome in rats. Front Pharmacol 2020; 11:1305-1315.
30. Duh K, Funaro MG, DeGouveia W, Bahlani S, Pappas D, Najjar S, et al. Crosstalk between the immune system and neural pathways in interstitial cystitis/bladder pain syndrome. Discov Med 2018; 25:243-250.
31. Juszczak K, Adamowicz J, Zapała Ł, Kluz T, Adamczyk P, Wdowiak A, et al. Potentilla chinensis aqueous extract attenuates cyclophosphamide-induced hemorrhagic cystitis in rat model. Sci Rep 2022; 12:13076-13088.
32. Jhang JF, Wang HJ, Hsu YH, Birder LA, Kuo HC. Upregulation of neurotrophins and transforming growth factor-β expression in the bladder may lead to nerve hyperplasia and fibrosis in patients with severe ketamine-associated cystitis. Neurourol Urodyn 2019; 38:2303-2310.
33. Merrill L, Gonzalez EJ, Girard BM, Vizzard MA. Receptors, channels, and signalling in the urothelial sensory system in the bladder. Nat Rev Urol 2016; 13:193-204.
34. Koh SD, Lee H, Ward SM, Sanders KM. The mystery of the interstitial cells in the urinary bladder. Annu Rev Pharmacol Toxicol 2018; 58:603-623.
35. Vannucchi MG, Traini C. The telocytes/myofibroblasts 3-D network forms a stretch receptor in the human bladder mucosa. Is this structure involved in the detrusor overactive diseases? Ann Anat 2018; 218:118-123.
36. Mykoniatis I, Tsiakaras S, Samarinas M, Anastasiadis A, Symeonidis EN, Sountoulides P. Monoclonal antibody therapy for the treatment of interstitial cystitis. Biologics 2022; 16:47-55.
37. Klinger MB, Vizzard MA. Role of p75NTR in female rat urinary bladder with cyclophosphamide-induced cystitis. Am J Physiol Renal Physiol 2008; 295:F1778-1789.
38. Dias B, Serrão P, Cruz F, Charrua A. Effect of water avoidance stress on serum and urinary NGF levels in rats: Diagnostic and therapeutic implications for BPS/IC patients. Sci Rep 2019; 9:14113-14120.
39. Shen S, Al-Thumairy HW, Hashmi F, Qiao LY. Regulation of transient receptor potential cation channel subfamily V1 protein synthesis by the phosphoinositide 3-kinase/Akt pathway in colonic hypersensitivity. Exp Neurol 2017; 295:104-115.
40. Frias B, Charrua A, Avelino A, Michel MC, Cruz F, Cruz CD. Transient receptor potential vanilloid 1 mediates nerve growth factor-induced bladder hyperactivity and noxious input. BJU Int 2012; 110:E422-428.
41. Kayama Y, Shibata M, Takizawa T, Ibata K, Nakahara J, Shimizu T, et al. Signaling pathways relevant to nerve growth factor-induced upregulation of transient receptor potential M8 expression. Neuroscience 2017; 367:178-188.
42. Pian P, Bucchi A, Decostanzo A, Robinson RB, Siegelbaum SA. Modulation of cyclic nucleotide-regulated HCN channels by PIP(2) and receptors coupled to phospholipase C. Pflugers Arch 2007; 455:125-145.

آمار
تعداد مشاهده مقاله: 456
تعداد دریافت فایل اصل مقاله: 410