Peptide REF1 is a local wound signal promoting plant regeneration.

Plants frequently encounter wounding and have evolved an extraordinary regenerative capacity to heal the wounds. However, the wound signal that triggers regenerative responses has not been identified. Here, through characterization of a tomato mutant defective in both wound-induced defense and regeneration, we demonstrate that in tomato, a plant elicitor peptide (Pep), REGENERATION FACTOR1 (REF1), acts as a systemin-independent local wound signal that primarily regulates local defense responses and regenerative responses in response to wounding. We further identified PEPR1/2 ORTHOLOG RECEPTOR-LIKE KINASE1 (PORK1) as the receptor perceiving REF1 signal for plant regeneration. REF1-PORK1-mediated signaling promotes regeneration via activating WOUND-INDUCED DEDIFFERENTIATION 1 (WIND1), a master regulator of wound-induced cellular reprogramming in plants. Thus, REF1-PORK1 signaling represents a conserved phytocytokine pathway to initiate, amplify, and stabilize a signaling cascade that orchestrates wound-triggered organ regeneration. Application of REF1 provides a simple method to boost the regeneration and transformation efficiency of recalcitrant crops.

Moscatilin Reverses EMT Progression and its Resulting Enhanced Invasion and Migration by Affecting the TGF-ß Signaling Pathway in Bladder Cancer.

BACKGROUND: Bladder cancer metastasis is an essential process in the progression of muscle-invasive bladder cancer. EMT plays a crucial role in facilitating the spread of cancer cells. Identifying compounds that can inhibit these abilities of cancer cells is a significant international endeavor. OBJECTIVE: To explore the migration and invasion effect of Moscatilin on the bladder and clarify the mechanism of action Method: The anti-bladder cancer effect of Moscatilin was observed by a cell proliferation experiment. The migration and invasion of bladder cancer cells inhibited by Moscatilin were detected by Transwell and Wound healing. The effects of Moscatilin on EMT-related proteins E-cadherin, N-cadherin, Snail1, Vimentin, and TGF-ß signaling pathways were detected by Western blot, and nucleic acid levels were verified by qPCR Results: Our study revealed that Moscatilin reduced the viability of bladder cancer cells in vitro and impeded their migration and invasion in experimental settings. Furthermore, we observed that Moscatilin decreased the activation levels of active proteins, specifically Smad3, Samd2, and MMP2. Additionally, we found that moscatilin significantly reduced the expression level of TGF-ß and was also capable of reversing the overexpression effect of TGF-ß. Treatment with Moscatilin also led to significant inhibition of interstitial cell markers Ncadherin and Snail1, which are associated with EMT. CONCLUSION: These findings indicate that Moscatilin impedes the migration and invasion of bladder cancer cells by influencing cell survival, modulating TGF-ß/Smad signaling, and inhibiting EMT.

Targeting Thbs1 reduces bladder remodeling caused by partial bladder outlet obstruction via the FGFR3/p-FGFR3 pathway.

BACKGROUND: Partial bladder outlet obstruction (pBOO) may lead to bladder remodeling, including fibrosis and extracellular matrix (ECM) deposition. Despite the extensive research on the mechanisms underlying pBOO, potential therapeutic targets for the treatment of pBOO require further research. Dysregulated expression of thrombospondin-1 (Thbs1) has been reported in various human fibrotic diseases; however, its relationship with pBOO remains unclear. AIMS: Investigate the effects of Thbs1 on bladder remodeling caused by pBOO. METHODS: We established a pBOO model in Sprague-Dawley rats and performed urodynamic analyses to estimate functional changes in the bladder, validated the histopathological changes in the bladder by using haematoxylin-eosin and Masson's trichrome staining, identified key target genes by integrating RNA sequencing (RNA-seq) and bioinformatics analyses, validated the expression of related factors using Western blot analysis and RT-qPCR, and used immunofluorescence staining to probe the potential interaction factors of Thbs1. RESULTS: Urodynamic results showed that pressure-related parameters were significantly increased in rats with pBOO. Compared with the sham group, the pBOO group demonstrated significant increases in bladder morphology, bladder weight, and collagen deposition. Thbs1 was significantly upregulated in the bladder tissues of rats with pBOO, consistent with the RNA-seq data. Thbs1 upregulation led to increased expression of matrix metalloproteinase (MMP) 2, MMP9, and fibronectin (Fn) in normal human urinary tract epithelial cells (SV-HUC-1), whereas anti-Thbs1 treatment inhibited the production of these cytokines in TGF-ß1-treated SV-HUC-1. Further experiments indicated that Thbs1 affected bladder remodeling in pBOO via the fibroblast growth factor receptor 3 (FGFR3) pathway. CONCLUSIONS: Thbs1 plays a crucial role in bladder remodeling caused by pBOO. Targeting Thbs1 might alleviate ECM damage. Mechanistically, Thbs1 may function via the FGFR signaling pathway by regulating the FGFR3 receptor, identified as the most relevant disease target of pBOO, and FGF2 may be a mediator. These findings suggest that Thbs1 plays a role in BOO development and is a therapeutic target for this condition.