(015) Evaluating Actinidin’s Collagen-Degrading Effects in a Human Model of Peyronie’s Disease
Bibliographic record
Abstract
Abstract Introduction Peyronie’s Disease (PD) is a fibrotic disorder of the penile tunica albuginea that leads to collagen plaque formation, penile curvature, pain, and erectile dysfunction. With the withdrawal of collagenase Clostridium histolyticum from the Canadian market, treatment options are limited. TGF-β1 is known to promote fibrosis and is commonly elevated in PD plaques. Actinidin is a plant-derived enzyme that can degrade multiple collagen types. Our previous studies using a 3D PD plaque model demonstrated that actinidin can reduce collagen accumulation in vitro. This study examines the effects of actinidin on collagen I and III levels and cell viability in a TGF-β1-induced PD cell model. Objective To evaluate the effects of actinidin on collagen expression and cell viability in human PD fibroblasts stimulated with TGF-β1. Methods Primary fibroblast cells were isolated from human PD plaques (n=4) and treated with 10 ng/mL of TGF-β1 for 24 hours to induce a fibrotic phenotype. Cells were then treated with actinidin (1–20 mg/mL) for 24 hours. MTT assays were performed at 24 hours and 48 hours to assess viability. Collagen I and III levels were analyzed by western blot after 24 hours. Results were analyzed using one-way or two-way repeated measures ANOVA with Tukey’s post hoc comparisons. Results TGF-β1 significantly increased collagen I and III expression and cell viability at 24 hours. Actinidin reduced collagen I levels at 10 mg/mL and 20 mg/mL (p=0.014 and p=0.003, respectively). Collagen III levels were significantly reduced at 20 mg/mL (p=0.0138). In the MTT assay, TGF-β1 increased cell viability at 24 hours (p<0.0001), which was significantly reduced by actinidin at 20 mg/mL (p=0.0012). At 48 hours, actinidin at concentrations of 1 mg/mL and above significantly reduced viability compared to TGF-β1 (p<0.02). Conclusions Actinidin reduced collagen I and III expression and reversed TGF-β1-induced increases in cell viability in human PD fibroblasts. Higher concentrations (10–20 mg/mL) were most effective. These findings suggest actinidin may offer a potential therapeutic strategy for PD by targeting collagen buildup. Future work will investigate its proteolytic specificity and assess delivery methods for localized application. Disclosure Yes, this is sponsored by industry/sponsor: KiwiEnzyme.com Ltd Clarification: No industry support in study design or execution
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".