Search results for "tissue homeostasi"
showing 10 items of 61 documents
A stress-responsive miRNA regulates BMP signaling to maintain tissue homeostasis
2021
Adult organisms must sense and adapt to environmental fluctuations. In high-turnover tissues such as the intestine, these adaptive responses require rapid changes in gene expression that, in turn, likely involve posttranscriptional gene control. However, intestinal-tissue-specific microRNA (miRNA)-mediated regulatory pathways remain unexplored. Here, we report the role of an intestinal-specific miRNA, miR-958, that non-cell autonomously regulates stem cell numbers during tissue homeostasis and regeneration in the Drosophila adult midgut. We identify its downstream target cabut, the Drosophila ortholog of mammalian KLF10/11 transcription factors, which mediates this miR-958 function by promo…
The regulation of efferocytosis signaling pathways and adipose tissue homeostasis in physiological conditions and obesity: Current understanding and …
2022
Obesity is associated with changes in the resolution of acute inflammation that contribute to the clinical complications. The exact mechanisms underlying unresolved inflammation in obesity are not fully understood. Adipocyte death leads to pro-inflammatory adipose tissue macrophages, stimulating additional adipocyte apoptosis. Thus, a complex and tightly regulated process to inhibit inflammation and maintain homeostasis after adipocyte apoptosis is needed to maintain health. In normal condition, a specialized phagocytic process (efferocytosis) performs this function, clearing necrotic and apoptotic cells (ACs) and controlling inflammation. For efficient and continued efferocytosis, phagocyt…
Negative regulators of integrin activity
2012
Integrins are heterodimeric transmembrane adhesion receptors composed of α- and β-subunits. They are ubiquitously expressed and have key roles in a number of important biological processes, such as development, maintenance of tissue homeostasis and immunological responses. The activity of integrins, which indicates their affinity towards their ligands, is tightly regulated such that signals inside the cell cruicially regulate the switching between active and inactive states. An impaired ability to activate integrins is associated with many human diseases, including bleeding disorders and immune deficiencies, whereas inappropriate integrin activation has been linked to inflammatory disorders…
Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool.
2015
Tissue homeostasis is achieved through a balance of cell production (growth) and elimination (regression). In contrast to tissue growth, the cells and molecular signals required for tissue regression remain unknown. To investigate physiological tissue regression, we use the mouse hair follicle, which cycles stereotypically between phases of growth and regression while maintaining a pool of stem cells to perpetuate tissue regeneration. Here we show by intravital microscopy in live mice that the regression phase eliminates the majority of the epithelial cells by two distinct mechanisms: terminal differentiation of suprabasal cells and a spatial gradient of apoptosis of basal cells. Furthermor…
Interleukin-33-Dependent Innate Lymphoid Cells Mediate Hepatic Fibrosis
2013
SummaryLiver fibrosis is a consequence of chronic liver diseases and thus a major cause of mortality and morbidity. Clinical evidence and animal studies suggest that local tissue homeostasis is disturbed due to immunological responses to chronic hepatocellular stress. Poorly defined stress-associated inflammatory networks are thought to mediate gradual accumulation of extracellular-matrix components, ultimately leading to fibrosis and liver failure. Here we have reported that hepatic expression of interleukin-33 (IL-33) was both required and sufficient for severe hepatic fibrosis in vivo. We have demonstrated that IL-33’s profibrotic effects related to activation and expansion of liver resi…
Collagen biology and non‐invasive biomarkers of liver fibrosis
2020
There is an unmet need for high-quality liquid biomarkers that can safely and reproducibly predict the stage of fibrosis and the outcomes of chronic liver disease (CLD). The requirement for such markers has intensified because of the high global prevalence of diseases such as non-alcoholic fatty liver disease (NAFLD). In particular, there is a need for diagnostic and prognostic tools, as well as predictive biomarkers that reflect the efficacy of interventions, as described by the BEST criteria (Biomarkers, EndpointS, and other Tools Resource). This review covers the various liver collagens, their functional role in tissue homeostasis and delineates the common nomenclature for biomarkers bas…
Regulation of ERK1/2 activity upon contact inhibition in fibroblasts.
2011
Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo. Despite its generally accepted importance for maintaining tissue homeostasis knowledge about the underlying molecular mechanisms of contact inhibition is still scarce. Since the MAPK ERK1/2 plays a pivotal role in the control of proliferation, we investigated regulation of ERK1/2 phosphorylation which is downregulated in confluent NIH3T3 cultures. We found a decrease in upstream signaling including phosphorylation of the growth factor receptor adaptor protein ShcA and the MAPK kinase MEK1/2 in confluent compared to exponentially growing cultures whereas involvement of ERK1/2 phosphatases in ERK1/2 inact…
Involvement of the transcription factor FoxM1 in contact inhibition
2012
Contact inhibition is a crucial mechanism regulating proliferation in vitro and in vivo. Although it is generally accepted that contact inhibition plays a pivotal role in maintaining tissue homeostasis, the molecular mechanisms of contact inhibition are still not fully understood. FoxM1 is known as a proliferation-associated transcription factor and is upregulated in many cancer types. Vice versa, anti-proliferative signals, such as TGF-β and differentiation signals decrease FoxM1 expression. Here we investigated the role of FoxM1 in contact inhibition in fibroblasts. We show that protein expression of FoxM1 is severely and rapidly downregulated upon contact inhibition, probably by inhibiti…
Hepatocellular expression of a dominant-negative mutant TGF-β type II receptor accelerates chemically induced hepatocarcinogenesis
2001
The potent growth-inhibitory activity of cytokines of the transforming growth factor-beta (TGF-beta) superfamily and their widespread expression in epithelia suggest that they may play an important role in the maintenance of epithelial homeostasis. To analyse TGF-beta mediated tumor suppressor activity in the liver, we generated transgenic mice overexpressing a dominant negative type II TGF-beta receptor in hepatocytes under control of the regulatory elements of the human C-reactive protein gene promoter. Transgenic animals exhibited constitutive and liver-specific transgene expression. The functional inactivation of the TGF-beta signaling pathway in transgenic hepatocytes was shown by redu…
Regulation of cell-to-cell communication in non-tumorigenic and malignant human prostate epithelial cells.
2002
BACKGROUND Gap-junction-mediated intercellular communication (GJIC) is required for normal development and tissue homeostasis. However, the role of GJIC in human prostate carcinogenesis and progression remains ill-defined. METHODS The ability of hormones, anti-hormones, and the anti-hypertensive drug, forskolin, to restore GJIC in non-tumorigenic (RWPE-1 and PWR-1E) and malignant (RWPE-2, LNCaP, DU-145) human prostate epithelial cell lines, was examined by Scrape-Loading/Dye Transfer (SL/DT) and Fluorescence Recovery After Photobleaching (FRAP) methods using an Ultima laser cytometer. RESULTS Results from both assays show that PWR-1E, RWPE-2, LNCaP, and DU-145 cells have weak or absent GJIC…