Fibrillins are the major components of microfibrils in the extracellular matrix of elastic and non-elastic tissues. Fibrillin-1 contains one evolutionarily conserved RGD sequence that mediates cell-matrix interactions through cell-surface integrins. Here, we present a novel paradigm how extracellular fibrillin-1 controls cellular function through integrin-mediated microRNA regulation. Comparative mRNA studies by global microarray analysis identified growth factor activity, actin binding and integrin binding as the most important functional groups that are regulated upon fibrillin-1 binding to dermal fibroblasts. Many of these mRNAs are targets of miRNAs that were identified when RNA from the fibrillin-1-ligated fibroblasts was analyzed by a miRNA microarray. The expression profile was specific to fibrillin-1 since interaction with fibronectin displayed a partially distinct profile. The importance of selected miRNAs for the regulation of the identified mRNAs was suggested by bioinformatics prediction and the interactions between miRNAs and mRNAs were experimentally validated. Functionally, we show that miR-503 controls p-Smad2-dependent TGF-β signaling, and that miR-612 and miR-3185 are involved in the focal adhesion formation regulated by fibrillin-1. In conclusion, we demonstrate that fibrillin-1 interaction with fibroblasts regulates miRNA expression profiles which in turn control critical cell functions.
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http://dx.doi.org/10.1016/j.jmb.2018.11.021 | DOI Listing |
J Exp Clin Cancer Res
January 2025
Mabwell (Shanghai) Bioscience Co., Ltd, Shanghai, 201210, China.
Background: Targeting the TGF-β pathway in tumor therapy has proven challenging due to the highly context-dependent functions of TGF-β. Integrin αvβ8, a pivotal activator of TGF-β, has been implicated in TGF-β signaling within tumors, as demonstrated by the significant anti-tumor effects of anti-αvβ8 antibodies. Nevertheless, the expression profile of αvβ8 remains a subject of debate, and the precise mechanisms underlying the anti-tumor effects of anti-αvβ8 antibodies are not yet fully elucidated.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
Research Institute for Prevention of Non-Communicable Diseases, Cellular and Molecular Research Center, Qazvin University of Medical Sciences, Qazvin, Iran. Electronic address:
Integrin αvβ3, a primary cell-adhesion receptor, plays a crucial role in various biological processes, including angiogenesis, pathological neovascularization, and tumor metastasis. Its expression increases during tumor angiogenesis. The insulin-like growth factor 1 receptor (IGF1R) is a transmembrane protein that stimulates vital signaling pathways, promoting cancer cell growth, survival, and metabolism.
View Article and Find Full Text PDFBiochem Biophys Res Commun
December 2024
Department of Biological Sciences, Faculty of Science, Hokkaido University, Kita 10 Nishi 8, Kita-ku, Sapporo, Hokkaido, 060-0810, Japan.
During avian germ cell formation, primordial germ cells (PGCs) differentiate into prospermatogonia in testicular seminiferous tubules or into oogonia in the ovarian cortex in late-stage embryos. Although estrogenic endocrine-disrupting chemicals (EDCs) have been suggested to affect the differential fate of avian germ cells, there is currently no established method to examine the effects of EDCs on the differentiation potential of germline cells due to large amount of unidentified proteins present in avian germ cells. Regarding reliable molecular probes for the detection of germ cells that differentiated from the PGCs of Japanese quail, the prospermatogonium and oogonium, respectively, integrin beta1 (ITGB1), insulin-like growth factor 2-binding protein 1 (IGF2BP1), and stimulated by retinoic acid 8 (STRA8) were identified as marker proteins by RNA-seq and liquid chromatography tandem mass spectrometry analyses.
View Article and Find Full Text PDFFront Immunol
January 2025
Department of Medicine, Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, United States.
Nat Commun
December 2024
College of Life Sciences, Inner Mongolia Agriculture University, Hohhot, Inner Mongolia, P. R. China.
Zika virus (ZIKV) infection can result in a birth defect of the brain called microcephaly and other severe fetal brain defects. ZIKV enters the susceptible host cells by endocytosis, which is mediated by the interaction of the envelope (E) glycoprotein with cellular surface receptor molecules. However, the cellular factors that used by the ZIKV to gain access to host cells remains elusive.
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