Academic Journal
Myostatin-dependent detrusor remodelling mediates contractility impairment in diabetic rats' bladder - a maximal elastance analysis.
| Τίτλος: | Myostatin-dependent detrusor remodelling mediates contractility impairment in diabetic rats' bladder - a maximal elastance analysis. |
|---|---|
| Συγγραφείς: | Lai CY; Institute of Biomedical Sciences, Mackay Medical College, New Taipei, Taiwan., Lau HH; Department of Medicine, Mackay Medical College, New Taipei, Taiwan.; Division of Urogynecology, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan., Hsieh MC; Department of Medicine, Mackay Medical College, New Taipei, Taiwan., Peng HY; Department of Medicine, Mackay Medical College, New Taipei, Taiwan., Chou D; Department of Medicine, Mackay Medical College, New Taipei, Taiwan., Su TH; Department of Medicine, Mackay Medical College, New Taipei, Taiwan.; Division of Urogynecology, Department of Obstetrics and Gynecology, Mackay Memorial Hospital, Taipei, Taiwan., Lin TB; Institute of Translational Medicine and New Drug Development, College of Medicine, China Medical University, Taichung, Taiwan.; Department of Physiology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.; Graduate Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, Taipei, Taiwan. |
| Πηγή: | The Journal of physiology [J Physiol] 2026 Oct; Vol. 604 (20), pp. 8428-8449. Date of Electronic Publication: 2026 Sep 18. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Cambridge Univ. Press Country of Publication: England NLM ID: 0266262 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1469-7793 (Electronic) Linking ISSN: 00223751 NLM ISO Abbreviation: J Physiol Subsets: MEDLINE |
| Imprint Name(s): | Publication: Oxford : Blackwell : Cambridge Univ. Press Original Publication: London, Cambridge Univ. Press. |
| Ιατρικοί όροι (MeSH): | Urinary Bladder*/physiopathology , Urinary Bladder*/metabolism , Urinary Bladder*/physiology , Myostatin*/metabolism , Myostatin*/physiology , Diabetes Mellitus, Experimental*/physiopathology , Diabetes Mellitus, Experimental*/metabolism , Muscle, Smooth*/physiopathology , Muscle, Smooth*/metabolism , Muscle Contraction*, Myosin Heavy Chains/metabolism ; Animals ; Female ; Rats, Sprague-Dawley ; Rats |
| Περίληψη: | The role of myostatin, an endogenous myokine mediating the pathological progression of myopathy, in contractility impairments of the chronically diabetic bladder remains unclear. This study examined whether maximal elastance (mE) reliably and validly assesses bladder contractility in vivo and investigated the role of myostatin-associated tissue remodelling in the contractility deficits in diabetic bladder. Eighty-three female Sprague-Dawley rats were assigned to control (CON), streptozotocin-treated (STZ; 30 mg/kg twice, i.p.) and STZ with non-specific IgG (STZ + IgG; 2 mg/kg, i.p.) or Myo-029 (a myostatin-neutralizing antibody; STZ + MYO; 2 mg/kg, i.p.). The slope of the end-emission pressure-volume relationship obtained from pressure-volume analysis was calculated as mE. mE remained relatively constant under altered preload and afterload but increased dose dependently with muscarine infusion (10 and 100 µM, 0.002 mL/min, i.a.) and decreased with atropine infusion (10 and 100 µM, 0.002 mL/min, i.a.). Compared to CON the STZ group showed decreased mE, reduced muscle-to-collagen ratio, increased myostatin expression, decreased myosin heavy chain 11 (MHC 11) and smoothelin expressions, as well as upregulated α-smooth muscle actin (SMA) and collagen type I alpha 1 (COL1A1) expressions. Treatment with Myo-029 in STZ animals reversed the reductions in the MHC 11 and smoothelin expressions, muscle-to-collagen ratio and mE, as well as the STZ-upregulated SMA and COL1A1 expression. Collectively mE effectively assessed bladder contractility in vivo. Moreover myostatin contributes to diabetes-associated deficits in bladder contractility by regulating detrusor remodelling, suggesting that myostatin may represent a potential therapeutic target for diabetes-associated cystopathy. KEY POINTS: Developing a methodology capable of precisely assessing bladder contractility in vivo is warranted to elucidate the underlying pathophysiology of bladder contractility impairments. The pathological progression of diabetic cystopathy has been linked to myogenic dysfunction of the detrusor, resulting in impaired bladder contractility. Maximal elastance (mE) is a bladder contractility-sensitive parameter that is independent of bladder preload and afterload. Bladders from long-standing diabetic rats exhibit diminished contractility, accompanied by upregulation of myostatin and downregulation of myosin heavy chain 11 and smoothelin. Administration of a myostatin-specific neutralizing antibody in diabetic rats reversed diabetes-associated downregulation of myosin heavy chain 11 and smoothelin, as well as bladder contractility impairment. mE effectively assessed bladder contractility in vivo. Moreover myostatin contributes to diabetes-associated deficits in bladder contractility by regulating myostatin-dependent detrusor remodelling, suggesting that myostatin may represent a potential therapeutic target for diabetic cystopathy. (© 2026 The Author(s). The Journal of Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.) |
| References: | Nature. 1997 May 1;387(6628):83-90. (PMID: 9139826) Trends Pharmacol Sci. 2006 Sep;27(9):492-7. (PMID: 16870270) Front Pharmacol. 2021 May 26;12:657959. (PMID: 34122078) J Urol. 2009 Dec;182(6 Suppl):S18-26. (PMID: 19846137) Bladder (San Franc). 2023 Jan 30;10:e21200001. (PMID: 37006949) Int J Biochem Cell Biol. 2013 Oct;45(10):2333-47. (PMID: 23721881) Bioengineering (Basel). 2023 Jul 19;10(7):. (PMID: 37508880) Biomed Eng Lett. 2024 Dec 30;15(2):357-365. (PMID: 40026886) Bioengineering (Basel). 2024 Aug 28;11(9):. (PMID: 39329617) Crit Care. 2016 Sep 10;20:270. (PMID: 27613430) Front Bioeng Biotechnol. 2022 Aug 19;10:912602. (PMID: 36061421) Circulation. 1987 Aug;76(2):343-56. (PMID: 3608122) Neuroendocrinology. 2013;98(4):267-80. (PMID: 24458095) N Engl J Med. 1993 Sep 30;329(14):977-86. (PMID: 8366922) J Cell Physiol. 1999 Jul;180(1):1-9. (PMID: 10362012) Dis Markers. 2021 Jan 13;2021:6644631. (PMID: 33520013) Neurourol Urodyn. 2007;26(6):814-9. (PMID: 17455274) Int J Urol. 2012 Mar;19(3):216-28. (PMID: 22233177) Front Neurosci. 2024 Aug 07;18:1432616. (PMID: 39170685) Lancet. 2022 Nov 19;400(10365):1803-1820. (PMID: 36332637) Am J Physiol. 1979 Mar;236(3):H498-505. (PMID: 426086) Low Urin Tract Symptoms. 2019 Sep;11(4):232-240. (PMID: 31207098) Front Bioeng Biotechnol. 2026 Jan 12;13:1677779. (PMID: 41602457) Diabetes Care. 2005 Jan;28(1):177-85. (PMID: 15616253) Science. 2002 May 24;296(5572):1486-8. (PMID: 12029139) World J Urol. 1995;13(1):30-3. (PMID: 7773315) J Minim Invasive Gynecol. 2024 Dec;31(12):1034-1040. (PMID: 39233274) Int J Urol. 2008 Aug;15(8):681-7. (PMID: 18462357) Neurourol Urodyn. 2021 Nov;40(8):1889-1899. (PMID: 34453858) Neurourol Urodyn. 2023 Feb;42(2):445-452. (PMID: 36519669) Clin Transl Sci. 2016 Dec;9(6):302-310. (PMID: 27700008) Int J Mol Sci. 2023 Feb 24;24(5):. (PMID: 36901894) Neurourol Urodyn. 2020 Jun;39(5):1304-1312. (PMID: 32293055) Biochem Biophys Res Commun. 2003 Jan 24;300(4):965-71. (PMID: 12559968) Urology. 2011 Mar;77(3):699-705. (PMID: 21195463) J Diabet Complications. 1988 Jul-Sep;2(3):133-9. (PMID: 2975663) Arch Ital Urol Androl. 2023 Mar 13;95(1):11072. (PMID: 36924376) Sci Rep. 2017 Apr 13;7:46362. (PMID: 28406165) Int Neurourol J. 2012 Dec;16(4):181-6. (PMID: 23346484) Vascul Pharmacol. 2006 Oct;45(4):221-6. (PMID: 16891158) Front Pharmacol. 2010 Nov 16;1:136. (PMID: 21833175) BJU Int. 2011 Jun;107(12):1988-93. (PMID: 21087392) Int J Mol Sci. 2022 Apr 11;23(8):. (PMID: 35457038) N Engl J Med. 2004 Jun 24;350(26):2682-8. (PMID: 15215484) |
| Grant Information: | MOST 109-2320-B-715-005 National Science and Technology Council; MOST 108-2320-B-715-002-MY3 National Science and Technology Council; 108-2314-B-715-004-MY3 National Science and Technology Council; NSTC 113-2314-B-715-010 National Science and Technology Council; NSTC 113-2314-B-715-001 National Science and Technology Council; 114-2314-B-715-002 National Science and Technology Council; 114-2221-E-038-005 National Science and Technology Council; NSTC 115-2221-E-038-002 National Science and Technology Council |
| Contributed Indexing: | Keywords: bladder; end‐emission pressure–volume relationship; maximal elastance; thermodynamic; transforming growth factor |
| Substance Nomenclature: | 0 (Myostatin) EC 3.6.4.1 (Myosin Heavy Chains) |
| Entry Date(s): | Date Created: 20260918 Date Completed: 20261016 Latest Revision: 20261019 |
| Update Code: | 20261019 |
| PubMed Central ID: | PMC13674209 |
| DOI: | 10.1113/JP291025 |
| PMID: | 42758701 |
| Βάση Δεδομένων: | MEDLINE |
καταχωρήστε σχόλιο πρώτοι!