Reduced granulation tissue and wound strength in the absence of α11β1 integrin.

Previous wound healing studies have failed to define a role for either α1β1 or α2β1 integrin in fibroblast-mediated wound contraction, suggesting the involvement of another collagen receptor in this process. Our previous work demonstrated that the integrin subunit α11 is highly induced during wound healing both at the mRNA and protein level, prompting us to investigate and dissect the role of the integrin α11β1 during this process. Therefore, we used mice with a global ablation of either α2 or α11 or both integrin subunits and investigated the repair of excisional wounds.

Role of integrins in the periodontal ligament: organizers and facilitators.

The periodontal ligament is the tissue that connects teeth to bone. The periodontal ligament is a fascinating tissue from a cell biologist's point of view, and because of its special properties and stem-cell content it has also come into the limelight in emerging fields of regenerative medicine. An increased range of genetically modified mouse models offer new tools for studying molecular mechanisms of tooth development.

α11β1 integrin-mediated MMP-13-dependent collagen lattice contraction by fibroblasts: evidence for integrin-coordinated collagen proteolysis.

We have previously determined that integrin α11β1 is required on mouse periodontal ligament (PDL) fibroblasts to generate the force needed for incisor eruption. As part of the phenotype of α11(-/-) mice, the incisor PDL (iPDL) is thickened, due to disturbed matrix remodeling. To determine the molecular mechanism behind the disturbed matrix dynamics in the PDL we crossed α11(-/-) mice with the Immortomouse and isolated immortalized iPDL cells.

Use of siRNA in dental tissue-derived cell cultures: integrin knockdown in fibroblasts.

Short (or small) interfering RNAs (siRNAs) are double-stranded RNA molecules about 21-25 nucleotides long that have the capacity to disrupt the activity of genes on a posttranscriptional level. This sequence homology-driven gene silencing capacity has been utilized by researchers to selectively block the translation of mRNA to proteins in order to study specific gene functions and identify target molecules. Importantly, siRNAs have the potential to be used in treatment of disease.

Prognostic gene-expression signature of carcinoma-associated fibroblasts in non-small cell lung cancer.

The tumor microenvironment strongly influences cancer development, progression, and metastasis. The role of carcinoma-associated fibroblasts (CAFs) in these processes and their clinical impact has not been studied systematically in non-small cell lung carcinoma (NSCLC). We established primary cultures of CAFs and matched normal fibroblasts (NFs) from 15 resected NSCLC.

Mutation in the heparan sulfate biosynthesis enzyme EXT1 influences growth factor signaling and fibroblast interactions with the extracellular matrix.

Heparan sulfate (HS) chains bind and modulate the signaling efficiency of many ligands, including members of the fibroblast growth factor (FGF) and platelet-derived growth factor families. We previously reported the structure of HS synthesized by embryonic fibroblasts from mice with a gene trap mutation of Ext1 that encodes a glycosyltransferase involved in HS chain elongation. The gene trap mutation results in low expression of Ext1, and, as a consequence, HS chain length is substantially reduced.

Integrins.

Integrins are cell adhesion receptors that are evolutionary old and that play important roles during developmental and pathological processes. The integrin family is composed of 24 alphabeta heterodimeric members that mediate the attachment of cells to the extracellular matrix (ECM) but that also take part in specialized cell-cell interactions. Only a subset of integrins (8 out of 24) recognizes the RGD sequence in the native ligands.

Identification of the first prokaryotic collagen sequence motif that mediates binding to human collagen receptors, integrins alpha2beta1 and alpha11beta1.

Many pathogenic bacteria interact with human integrins to enter host cells and to augment host colonization. Group A Streptococcus (GAS) employs molecular mimicry by direct interactions between the cell surface streptococcal collagen-like protein-1 (Scl1) and the human collagen receptor, integrin alpha2beta1. The collagen-like (CL) region of the Scl1 protein mediates integrin-binding, although, the integrin binding motif was not defined.

Alpha11 beta1 integrin-dependent regulation of periodontal ligament function in the erupting mouse incisor.

The fibroblast integrin alpha11beta1 is a key receptor for fibrillar collagens. To study the potential function of alpha11 in vivo, we generated a null allele of the alpha11 gene. Integrin alpha11(-/-) mice are viable and fertile but display dwarfism with increased mortality, most probably due to severely defective incisors.

Tandem Sp1/Sp3 sites together with an Ets-1 site cooperate to mediate alpha11 integrin chain expression in mesenchymal cells.

Alpha11beta1 integrin is a collagen receptor, which is expressed in a highly regulated manner in a specific subset of ectomesenchymally and mesodermally derived cells. We previously established that a 3 kb region upstream of the transcription start site of the ITGA11 gene efficiently induced alpha11 transcription in a cell-type specific manner. Using the human fibrosarcoma cell line HT1080 and human skin fibroblasts, we now report that the majority of the activity in the proximal promoter resides in a region spanning nt +25 to nt -176.