We used rat experimental myocardial infarction to study the ultrastructural recovery, especially neo-angiogenesis in the infarction border zone. We were interested in the possible role(s) of telocytes (TCs), a novel type of interstitial cell very recently discovered in myocardim (see ). Electron microscopy, immunocytochemistry and analysis of several proangiogenic microRNAs provided evidence for TC involvement in neo-angiogenesis after myocardial infarction. Electron microscopy showed the close spatial association of TCs with neoangiogenetic elements. Higher resolution images provided the following information: (a) the intercellular space between the abluminal face of endothelium and its surrounding TCs is frequently less than 50 nm; (b) TCs establish multiple direct nanocontacts with endothelial cells, where the extracellular space seems obliterated; such nanocontacts have a length of 0.4–1.5 μm; (c) the absence of basal membrane on the abluminal face of endothelial cell. Besides the physical contacts (either nanoscopic or microscopic) TCs presumably contribute to neo-angiognesis via paracrine secretion (as shown by immunocytochemistry for VEGF or NOS2). Last but not least, TCs contain measurable quantities of angiogenic microRNAs (e.g. let-7e, 10a, 21, 27b, 100, 126-3p, 130a, 143, 155, 503). Taken together, the direct (physical) contact of TCs with endothelial tubes, as well as the indirect (chemical) positive influence within the ‘angiogenic zones’, suggests an important participation of TCs in neo-angiogenesis during the late stage of myocardial infarction.

BCL11 genes play crucial roles in lymphopoiesis and have been associated with hematopoietic malignancies. Specifically, disruption of the BCL11B (B-cell chronic lymphocytic leukemia/lymphoma 11B) locus is linked to T-cell acute lymphoblastic leukemia, and the loss of heterozygosity in mice results in T-cell lymphoma. BCL11 proteins are related C 2 H 2 zinc-finger transcription factors that act as transcriptional repressors. Here, we demonstrate the association of the endogenous BCL11B with the nucleosome remodeling and histone deacetylase (NuRD) complex, one of the major transcriptional corepressor complexes in mammalian cells. BCL11B complexes from T lymphocytes possess trichostatin A-sensitive histone deacetylase activity, confirming the functionality of the complexes. Analysis of the BCL11B-NuRD association demonstrated that BCL11B directly interacted with the metastasis-associated proteins MTA1 and MTA2 through the amino-terminal region. We provide evidence for the functional requirement of MTA1 in transcriptional repression mediated by BCL11B through the following: (1) overexpression of MTA1 enhanced the transcriptional repression mediated by BCL11B, (2) knockdown of MTA1 expression by small interfering RNA inhibited BCL11B transcriptional repression activity and (3) MTA1 was specifically recruited to a BCL11B targeted promoter. Taken together, these data support the hypothesis that the NuRD complex mediates transcriptional repression function of BCL11B.

Telocytes (TCs) are interstitial cells with telopodes – very long prolongations that establish intercellular contacts with various types of cells. Telocytes have been found in many organs and various species and have been characterized ultrastructurally, immunophenotypically and electrophysiologically (http://www.telocytes.com). Telocytes are distributed through organ stroma forming a three-dimensional network in close contacts with blood vessels, nerve bundles and cells of the local immune system. Moreover, it has been shown that TCs express a broad range of microRNAs, such as pro-angiogenic and stromal-specific miRs. In this study, the gene expression profile of murine lung TCs is compared with other differentiated interstitial cells (fibroblasts) and with stromal stem/progenitor cells. More than 2000 and 4000 genes were found up- or down-regulated, respectively, in TCs as compared with either MSCs or fibroblasts. Several components or regulators of the vascular basement membrane are highly expressed in TCs, such as Nidogen, Collagen type IV and Tissue Inhibitor of Metalloproteinase 3 (TIMP3). Given that TCs locate in close vicinity of small vessels and capillaries, the data suggest the implication of TCs in vascular branching. Telocytes express also matrix metalloproteases Mmp3 and Mmp10, and thus could regulate extracellular matrix during vascular branching and de novo vessel formation. In conclusion, our data show that TCs are not fibroblasts, as the ultrastructure, immunocytochemistry and microRNA assay previously indicated. Gene expression profile demonstrates that TCs are functionally distinct interstitial cells with specific roles in cell signalling, tissue remodelling and angiogenesis.

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