SnoN residue (1-366) attenuates hypertrophic scars through resistance to transforming growth factor-ß1-induced degradation.

Hypertrophic scars (HSs) are characterized by fibroblast hyperproliferation and excessive matrix deposition. During wound healing, transforming growth factor (TGF)-ß1/Smad signaling acts as a key regulator. As a transcriptional corepressor of TGF-ß1/Smads, SnoN is expressed at low levels in many fibrotic diseases due to TGF-ß1/Smad-induced degradation. SnoN residue (1-366; SR) is resistant to TGF-ß1-induced degradation. However, the expression and role of SR in HSs are unknown. Here, we inhibited TGF-ß1/Smad signaling via overexpression of SR to block fibroblast transdifferentiation, proliferation, and collagen deposition during HS formation. Our results showed that SnoN was downregulated in HS fibroblasts (HSFs) owing to TGF-ß1/Smad-induced degradation. Overexpression of SR in normal human dermal fibroblasts (NHDFs) and HSFs successfully blocked phosphorylation of Smad2 and Smad3, thereby inhibiting NHDF transdifferentiation and HSF proliferation and reducing type I collagen (ColI) and type III collagen (ColIII) production and secretion. In addition, we applied overexpressed full-length SnoN (SF) and SR to wound granulation tissue in a rabbit model of HSs. SR reduced wound scarring, improved collagen deposition and arrangement of scar tissue, and decreased mRNA and protein expression of ColI, ColIII, and α-smooth muscle actin (α-SMA) more effectively than SF in vivo. These results suggest that SR could be a promising therapy for the prevention of HS.

SHCBP1 is over-expressed in breast cancer and is important in the proliferation and apoptosis of the human malignant breast cancer cell line.

BACKGROUND: SHC SH2-binding protein 1, a member of Src homolog and collagen homolog (Shc) family, has been recently identified in different contexts in unbiased screening assays. It has been reported to be over-expressed in several malignant cancers. METHODS: Immunohistochemistry of SHCBP1 on 128 breast cancer tissues and adjacent normal tissues were used to evaluate the prognostic significance of SHCBP1. Survival analyses were performed by Kaplan-Meier method. CRISPR/CAS9 method was used to knockout SHCBP1 expression. CRISPR/CAS9 technology was used to knockout SHCBP1 in 2 breast cancer cell lines. MTT assay, BrdU assay, colony formation assay, cell cycle assay and apoptosis analysis in MCF-7 and MDA-MB-231 cell lines were carried out to evaluate the effects of SHCBP1 on breast cancer in vitro. RESULTS: Immunohistochemical analysis revealed SHCBP1 was significantly up-regulated in breast cancer tissues compared with adjacent normal tissues (82 of 128, 64%). Over-expressed SHCBP1 was correlated with advanced clinical stage and poorer survival. Ablation of SHCBP1 inhibited the proliferation in vitro. SHCBP1 knockout increased cyclin-dependent kinase inhibitor p21, and decreased the Cyclin B1 and CDK1. CONCLUSION: Our study suggests SHCBP1 is dysregulated expressed in breast cancer and plays a critical role in cancer progression, which can be a potential prognosis predictor of breast cancer.

Cartilage Oligomeric Matrix Protein-Angiopoietin-1 Has a Protective Effect of Vascular Endothelial Barrier in Rat With Acute Necrotizing Pancreatitis.

OBJECTIVE: To investigate the protective effect of angiopoietin-1 (Ang-1) from capillary endothelial damage in rats with acute necrotizing pancreatitis (ANP). METHODS: 96 male Sprague-Dawley rats were randomly averaged and divided into control group, ANP group, Si-Ang-1 group, and COMP (cartilage oligomeric matrix protein)-Ang-1 group. Animals were killed at 6, 12, and 24 hours after molding. Levels of serum amylase, porcine endothelin 1, C-reactive protein, and Ang-1 were detected; histopathological changes in the pancreas were observed; capillary permeability and Ang-1 expression of the pancreatic tissue were detected by Evans Blue extravasation assay, immunohistochemistry, Western blot, and quantitative polymerase chain reaction. RESULTS: (1) Levels of serum amylase, C-reactive protein, and porcine endothelin-1 increased and level of Ang-1 decrease in the ANP group and Si-Ang-1 group compared with the control group, whereas COMP-Ang-1 group could improve the changes. (2) The order of pancreas pathological changes (mild to severe) is: control group, COMP-Ang-1 group, ANP group, and Si-Ang-1 group. (3) Capillary permeability of the pancreatic tissue in the COMP-Ang-1 group was lower than that in the ANP group. (4) Ang-1 mRNA and protein expression in the COMP-Ang-1 group was significantly higher than in the ANP group. CONCLUSIONS: COMP-Ang-1 can upregulate the expression of Ang-1 protein to promote angiogenesis and improve early inflammatory and pathological damage in ANP group.