scholarly journals The Preliminary Study of Effects of Tolfenamic Acid on Cell Proliferation, Cell Apoptosis, and Intracellular Collagen Deposition in Keloid FibroblastsIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Dan Yi ◽  
Ji Bihl ◽  
Mackenzie S. Newman ◽  
Yanfang Chen ◽  
Richard Simman
Keyword(s):  
Cell Proliferation ◽  
Cell Apoptosis ◽  
Collagen Type ◽  
Dose Range ◽  
Collagen Type I ◽  
Tolfenamic Acid ◽  
Type I ◽  
Preliminary Study ◽  
Intracellular Collagen ◽  
Keloid Fibroblasts

Keloid scarring is a fibroproliferative disorder due to the accumulation of collagen type I. Tolfenamic acid (TA), a nonsteroidal anti-inflammatory drug, has been found to potentially affect the synthesis of collagen in rats. In this preliminary study, we aimed to test the effects of TA on cell proliferation, cell apoptosis, and the deposition of intracellular collagen in keloid fibroblasts. Normal fibroblasts (NFs) and keloid fibroblasts (KFs) were obtained from human dermis tissue. Within the dose range 10−3–10−6 M and exposure times 24 h, 48 h, and 72 h, we found that 0.55 × 10−3 M TA at 48 h exposure exhibited significantly decreased cell proliferation in both NFs and KFs. Under these experimental conditions, we demonstrated that (1) TA treatment induced a remarkable apoptotic rate in KFs compared to NFs; (2) TA treatment reduced collagen production in KFs versus NFs; (3) TA treatment decreased collagen type I expression in KFs comparing to that of NFs. In summary, our data suggest that TA decreases cell proliferation, induces cell apoptosis, and inhibits collagen accumulation in KFs.

scholarly journals siRNA Knockdown of Tissue Inhibitor of Metalloproteinase-1 in Keloid Fibroblasts Leads to Degradation of Collagen Type I

2014 ◽  
Vol 134 (3) ◽  
pp. 818-826 ◽  
Author(s):  
Masayo Aoki ◽  
Koichi Miyake ◽  
Rei Ogawa ◽  
Teruyuki Dohi ◽  
Satoshi Akaishi ◽  
...  
Keyword(s):  
Collagen Type ◽  
Collagen Type I ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Type I ◽  
Tissue Inhibitor ◽  
Sirna Knockdown ◽  
Keloid Fibroblasts

scholarly journals Down-regulation of BRCA2 Expression by Collagen Type I Promotes Prostate Cancer Cell Proliferation

2005 ◽  
Vol 280 (23) ◽  
pp. 22482-22491 ◽  
Author(s):  
Loredana Moro ◽  
Arnaldo A. Arbini ◽  
Ersilia Marra ◽  
Margherita Greco
Keyword(s):  
Cell Proliferation ◽  
Cancer Cell ◽  
Prostate Carcinoma ◽  
Collagen Type ◽  
Carcinoma Cell ◽  
Collagen Type I ◽  
Type I ◽  
Cancer Cell Proliferation ◽  
Brca2 Protein ◽  
Prostate Carcinoma Cell

BRCA2 is a tumor suppressor gene that when mutated confers an increased susceptibility to developing breast and prostate carcinoma. Besides its role in mediating DNA repair, new evidence suggests that BRCA2 may also play a role in suppressing cancer cell growth. Because altered interactions between neoplastic cells and the surrounding extracellular matrix (ECM) play a pivotal role in unchecked cancer cell proliferation and metastatic progression, we hypothesized that the ECM may have an effect in BRCA2 expression. By using normal and prostate carcinoma cell lines, we demonstrated that although normal cells transiently increase BRCA2 protein levels when adhering to the ECM protein collagen type I (COL1), carcinoma cells exhibit a significant reduction in BRCA2 protein. This aberrant effect is independent from de novo protein synthesis and results from COL1-β1 integrin signaling through phosphatidylinositol (PI) 3-kinase leading to BRCA2 ubiquitination and degradation in the proteasome. BRCA2 protein depletion after cancer cell adhesion to COL1 or in small RNA interference assays triggers new DNA synthesis, a trophic effect that is abrogated by recombinant BRCA2 expression. Blocking or inhibiting β1 integrin, PI 3-kinase, or proteasome activity all have a negative effect on COL1-mediated DNA synthesis in cancer cells. In normal cells, the transient increase in BRCA2 expression is independent from β1 integrin or PI 3-kinase and has no effect in cell proliferation. In summary, these results unravel a novel mechanism whereby prostate carcinoma cell proliferation is enhanced by the down-regulation of BRCA2 expression when interacting with COL1, a major component of the ECM at osseous metastatic sites.

Collagen Type I α-1 Promotes Malignant Glioma Cell Proliferation and Is Associated with Glioma Prognosis

2021 ◽  
Vol 11 (3) ◽  
pp. 560-566
Author(s):  
Bruce Chunsik Im ◽  
Junjun Li ◽  
Henok Kessete Afewerky ◽  
Xiaobing Jiang
Keyword(s):  
Cell Proliferation ◽  
Cell Lines ◽  
Glioma Cell ◽  
Collagen Type ◽  
Collagen Type I ◽  
Low Grade ◽  
Type I ◽  
Mrna Levels ◽  
Protein Levels ◽  
Glioma Cell Proliferation

Collagen type I α-1 chain (COL1A1) is closely involved in the advancement of various tumors, yet the role of COL1A1 in the progression of glioma is not clear. Herein, we evaluated the effect of COL1A1 on glioma cell proliferation. The effect of COL1A1 on glioma cell proliferation was assessed through overexpression or knockdown of COL1A1. The CCK-8 and colony formation assays, as well as immunohistochemistry (IHC) were used to detect COL1A1 expression in different glioma grades. U-87MG as well as U-251MG cells were stably-inserted with lentivirus containing COL1A1 through transfection, we additionally used qRT-PCR as well as Western blot assay to validate their overexpression efficiencies. COL1A1 mRNA and protein levels were upregulated in the high-grade glioma (HGG) compared to the low-grade glioma (LGG). COL1A1 IHC score was remarkably higher in HGG than LGG. The staining index (SI) further showed that COL1A1 protein levels were higher in HGG than LGG. The Kaplan–Meier analysis showed that elevated COL1A1 mRNA levels were obviously correlated with lower overall survival (OS) and disease-free survival (DFS) for brain glioma patients. COL1A1 mRNA and protein levels were markedly upregulated in human glioma cell lines when compared with brain astrocyte cell lines. The high expression level of COL1A1 facilitated glioma cell proliferation. COL1A1 knockdown remarkably inhibited glioma cell proliferation. Thus, this research shows that COL1A1 promotes glioma cell proliferation and is closely related to glioma prognosis.

scholarly journals Inhibition of tyrosine kinase receptor signaling attenuates fibrogenesis in an ex vivo model of human renal fibrosis

2020 ◽  
Vol 318 (1) ◽  
pp. F117-F134 ◽  
Author(s):  
Emilia Bigaeva ◽  
Elisabeth G. D. Stribos ◽  
Henricus A. M. Mutsaers ◽  
Bram Piersma ◽  
Anna M. Leliveld ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Growth Factor ◽  
Tyrosine Kinase ◽  
Renal Fibrosis ◽  
Collagen Type ◽  
Growth Factor Receptor ◽  
Collagen Type I ◽  
Renal Tissue ◽  
Tyrosine Kinase Receptors ◽  
Type I

Poor translation from animal studies to human clinical trials is one of the main hurdles in the development of new drugs. Here, we used precision-cut kidney slices (PCKS) as a translational model to study renal fibrosis and to investigate whether inhibition of tyrosine kinase receptors, with the selective inhibitor nintedanib, can halt fibrosis in murine and human PCKS. We used renal tissue of murine and human origins to obtain PCKS. Control slices and slices treated with nintedanib were studied to assess viability, activation of tyrosine kinase receptors, cell proliferation, collagen type I accumulation, and gene and protein regulation. During culture, PCKS spontaneously develop a fibrotic response that resembles in vivo fibrogenesis. Nintedanib blocked culture-induced phosphorylation of platelet-derived growth factor receptor and vascular endothelial growth factor receptor. Furthermore, nintedanib inhibited cell proliferation and reduced collagen type I accumulation and expression of fibrosis-related genes in healthy murine and human PCKS. Modulation of extracellular matrix homeostasis was achieved already at 0.1 μM, whereas high concentrations (1 and 5 μM) elicited possible nonselective effects. In PCKS from human diseased renal tissue, nintedanib showed limited capacity to reverse established fibrosis. In conclusion, nintedanib attenuated the onset of fibrosis in both murine and human PCKS by inhibiting the phosphorylation of tyrosine kinase receptors; however, the reversal of established fibrosis was not achieved.

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