ArticleNeurourology and urodynamics2018
Relaxin-2 therapy reverses radiation-induced fibrosis and restores bladder function in mice.
Article in Neurourology and urodynamics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Precision-Cut Bladder Slices: A Novel Model for the Study of Bladder Fibrosis and Potential Anti-Fibrotic Agents.International journal of urology : official journal of the Japanese Urological Association · 2026Article
- Investigation of image-guided in vivo irradiation on voiding patterns and bladder contractility in female mice.Scientific reports · 2025Article
- Epithelial and mesenchymal compartments of the developing bladder and urethra display spatially distinct gene expression patterns.Developmental biology · 2025Article
- Assessment of lower urinary tract symptoms and their impact on quality of life following radiation therapy for bladder cancer.Bladder (San Francisco, Calif.) · 2025Article
- What do we really know about the external urethral sphincter?Continence (Amsterdam, Netherlands) · 2024Review
- Defining the molecular fingerprint of bladder and kidney fibroblasts.American journal of physiology. Renal physiology · 2023Review
- Studies of ultrastructure, gene expression, and marker analysis reveal that mouse bladder PDGFRAAmerican journal of physiology. Renal physiology · 2022Article
- Molecular Mechanisms and Key Processes in Interstitial, Hemorrhagic and Radiation Cystitis.Biology · 2022Review
- Increased extracellular matrix stiffness accompanies compromised bladder function in a murine model of radiation cystitis.Acta biomaterialia · 2022Article
- Benign prostatic hyperplasia/obstruction ameliorated using a soluble guanylate cyclase activator.The Journal of pathology · 2022Article
- Telmisartan inhibits bladder smooth muscle fibrosis in neurogenic bladder rats.Experimental and therapeutic medicine · 2022Article
- Targeting neurotrophin and nitric oxide signaling to treat spinal cord injury and associated neurogenic bladder overactivity.Continence (Amsterdam, Netherlands) · 2022Article
- Understanding Molecular Mechanisms and Identifying Key Processes in Chronic Radiation Cystitis.International journal of molecular sciences · 2022Review
- Molecular Changes in miRNA in Irradiated Rat Kidneys: Role of miR-34a and its Vascular Targets in the Notch Pathway.Radiation research · 2021Article
- Effects of an alpha-1d adrenoreceptor antagonist (naftopidil) on bladder dysfunction after radiotherapy in female rats.International urogynecology journal · 2021Article
- Voiding defects in acute radiation cystitis driven by urothelial barrier defect through loss of E-cadherin, ZO-1 and Uroplakin III.Scientific reports · 2021Article
- Contractile and Structural Properties of Detrusor from Children with Neurogenic Lower Urinary Tract Dysfunction.Biology · 2021Article
- Strategies to enhance monoclonal antibody uptake and distribution in solid tumors.Cancer biology & medicine · 2021Review
- Impact of prostatic radiation therapy on bladder contractility and innervation.Neurourology and urodynamics · 2021Article
- Irreversible Bladder Remodeling Induced by Fibrosis.International neurourology journal · 2021Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
aimTo determine the efficacy of human relaxin-2 (hRLX2) in reversing radiation-induced bladder fibrosis and lower urinary tract dysfunction (LUTD). Radiation cystitis is a consequence of radiotherapy for pelvic malignancies. Acutely, irradiation leads to reactive oxygen/nitrogen species in urothelial cells, apoptosis, barrier disruption, and inflammation. Chronically, this results in collagen deposition, bladder fibrosis, and attenuated storage and voiding functions. In severe cases, cystectomies are performed as current therapies do not reverse fibrosis.
methodsWe developed a mouse model for selective bladder irradiation (10 Gray; 1 Gy = 100 rads) resulting in chronic fibrosis within 6 weeks, with decreased bladder compliance, contractility, and overflow incontinence. Seven weeks post-irradiation, female C57Bl/6 mice were continuously infused with hRLX2 (400 μg/kg/day/14 days) or vehicle (saline) via subcutaneous osmotic pumps. Mice were evaluated in vivo using urine spot analysis, cystometrograms and external urethral sphincter electromyograms; and in vitro using length-tension measurements, Western blots, histology, and immunohistochemistry.
resultshRLX2 reversed fibrosis, decreased collagen content, improved bladder wall architecture, and increased bladder compliance, detrusor smooth muscle Cav1.2 expression and detrusor contractility in mice with chronic radiation cystitis. hRLX2 treatment outcomes were likely caused by the activation of RXFP1/2 receptors which are expressed on the detrusor.
conclusionhRLX2 may be a new therapeutic option for rescuing bladders with chronic radiation cystitis.
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