Subcutaneous lipoatrophy characteristically accompanies dermal fibrosis with de novo emergence of myofibroblasts such as in systemic sclerosis or scleroderma. Recently dermal adipocytes were shown to have the capacity to differentiate to myofibroblasts in an animal model. Transforming growth factor β can induce this phenomenon in vitro; however its in vivo significance is unclear. Because found in inflammatory zone 1 (FIZZ1) is an inducer of myofibroblast differentiation but an inhibitor of adipocyte differentiation, we investigated its potential role in adipocyte transdifferentiation to myofibroblast in dermal fibrosis. FIZZ1 caused significant and rapid suppression of the expression of fatty acid binding protein 4 and peroxisome proliferator-activated receptor-γ in adipocytes, consistent with dedifferentiation with loss of lipid and Oil Red O staining. The suppression was accompanied subsequently with stimulation of α-smooth muscle actin and type I collagen expression, indicative of myofibroblast differentiation. In vivo FIZZ1 expression was significantly elevated in the murine bleomycin-induced dermal fibrosis model, which was associated with significant reduction in adipocyte marker gene expression and subcutaneous lipoatrophy. Finally, FIZZ1 knockout mice exhibited significantly reduced bleomycin-induced dermal fibrosis with greater preservation of the subcutaneous fat than wild-type mice. These findings suggested that the FIZZ1 induction of adipocyte transdifferentiation to myofibroblast might be a key pathogenic mechanism for the accumulation of myofibroblasts in dermal fibrosis.
Last. John Varga(NU: Northwestern University)H-Index: 102
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Fibrosis of the skin and internal organs is the distinguishing pathologic hallmark of systemic sclerosis (SSc; scleroderma) and is responsible for its major complications (1,2). Skin fibrosis is caused by the presence of myofibroblasts, which are regarded as the primary fibrogenic effector cells in SSc driving excessive accumulation of fibrillar collagens and other extracellular matrix proteins in the dermis (3). Although multiple sources of myofibroblast precursors have been proposed, the origi...
PURPOSE OF REVIEW: To summarize the recent advances in understanding the novel cytokine pathways, intracellular signaling molecules, cell-fate decisions, cellular aging and senescence, and the cross-talk of effector cells and the extracellular matrix (ECM) in the pathogenesis of systemic sclerosis (SSc) fibrosis. RECENT FINDINGS: Studies from the animal models and human beings implicate novel molecular pathways such as Wnts, the chemokines, chemokine (C-X-C motif) ligand 4 and chemokine (C-C mot...
Adipocytes are intimately associated with the dermal compartment of the skin, existing in a specialized dermal depot and displaying dynamic changes in size during tissue homeostasis. However, the roles of adipocytes in cutaneous biology and disease are not well understood. Traditionally, adipocytes within tissues were thought to act as reservoirs of energy, as thermal, or as structural support. In this review, we discuss recent studies revealing the cellular basis of the dynamic development and ...
#1Tianju Liu(UM: University of Michigan)H-Index: 23
#2Hongfeng Yu(UM: University of Michigan)H-Index: 7
Last. Sem H. Phan(UM: University of Michigan)H-Index: 75
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FIZZ (found in inflammatory zone) 1, a member of a cysteine-rich secreted protein family, is highly induced in lung allergic inflammation and bleomycin induced lung fibrosis, and primarily expressed by airway and type II alveolar epithelial cells. This novel mediator is known to stimulate α-smooth muscle actin and collagen expression in lung fibroblasts. The objective of this study was to investigate the in vivo effects of FIZZ1 on the development of lung fibrosis by evaluating bleomycin-induced...
Obesity, defined as an excessive increase in white adipose tissue (WAT), is a global health epidemic. In obesity, WAT expands by increased adipocyte size (hypertrophy) and number (hyperplasia). The location and cellular mechanisms of WAT expansion greatly affect the pathogenesis of obesity. However, the cellular and molecular mechanisms regulating adipocyte size, number, and depot-dependent expansion in vivo remain largely unknown. This perspective summarizes previous work addressing adipocyte n...
Systemic sclerosis [scleroderma (SSc)]-associated skin fibrosis is characterized by increased fibrosis in the dermis and a reduction in the thickness of the subcutaneous adipose tissue layer. Although many studies have examined fibrosis in SSc, only a few studies have focused on the associated reduction in the thickness of the subcutaneous adipose tissue layer. In this study, we investigated the effects of SSc-induced fibrosis on adipose tissue. We found that bleomycin suppresses adipogenesis in...
Acute wound healing in the skin involves the communication of multiple cell types to coordinate keratinocyte and fibroblast proliferation and migration for epidermal and dermal repair. Many studies have focused on the interplay between hematopoietic cells, keratinocytes and fibroblasts during skin wound healing, yet the possible roles for other cell types within the skin, such as intradermal adipocytes, have not been investigated during this process. Here, we identify that adipocyte lineage cell...
Adipocytes have been suggested to arise from prospective progenitors of endothelial or haematopoietic origin. Rodeheffer and colleagues use lineage tracing to rule out that this is the case for white adipocytes, and show that they instead arise from CD24+ cells that are characterized by the expression of PdgfR (platelet-derived growth factor receptor).
Here, we explore the established and potential roles for intradermal adipose tissue in communication with hair follicle biology. The hair follicle delves deep into the rich dermal macroenvironment as it grows to maturity where it is surrounded by large lipid-filled adipocytes. Intradermal adipocytes regenerate with faster kinetics than other adipose tissue depots and in parallel with the hair cycle, suggesting an interplay exists between hair follicle cells and adipocytes. While adipocytes have ...
The discovery of the myofibroblast has opened new perspectives for the comprehension of the biological mechanisms involved in wound healing and fibrotic diseases. In recent years, many advances have been made in understanding important aspects of myofibroblast basic biological characteristics. This review summarizes such advances in several fields, such as the following: i) force production by the myofibroblast and mechanisms of connective tissue remodeling; ii) factors controlling the expressio...
Skin photoaging is mainly induced by ultraviolet (UV) irradiation and its manifestations include dry skin, coarse wrinkle, irregular pigmentation, and loss of skin elasticity. Dietary supplementation of nutraceuticals with therapeutic and preventive effects against skin photoaging has recently received increasing attention. This article aims to review the research progress in the cellular and molecular mechanisms of UV-induced skin photoaging. Subsequently, the beneficial effects of dietary comp...
#1Yong Sook Kim(Chonnam National University)H-Index: 25
#2Hyang Hee Cho(Chonnam National University)H-Index: 4
Last. Youngkeun Ahn(Chonnam National University)H-Index: 43
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Resistin-like alpha (Retnla) is a member of the resistin family and known to modulate fibrosis and inflammation. Here, we investigated the role of Retnla in the cardiac injury model. Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and was significantly preserved in the KO mice, while worsened in the TG group. Angiogenesis was substantially increased in the KO mice, and cardiomyocyte...
Adipose-derived stem cells (ADSCs) residing in the stromal vascular fraction (SVF) of white adipose tissue are recently emerging as an alternative tool for stem cell-based therapy in systemic sclerosis (SSc), a complex connective tissue disorder affecting the skin and internal organs with fibrotic and vascular lesions. Several preclinical and clinical studies have reported promising therapeutic effects of fat grafting and autologous SVF/ADSC-based local treatment for facial and hand cutaneous ma...
Abstract Inhalation of silica particles causes silicosis: an occupational lung disease characterized by persistent inflammation with granuloma formation that leads to tissue remodeling and impairment of lung function. Although silicosis has been studied intensely, little is known about the crucial cellular mechanisms that initiate and drive the process of inflammation and fibrosis. Recently, found in inflammatory zone 1 (FIZZ1) protein, produced by alveolar macrophages and fibroblasts have been ...
Summary Mature adipocytes store fatty acids and are a common component of tissue stroma. Adipocyte function in regulating bone marrow, skin, muscle, and mammary gland biology is emerging, but the role of adipocyte-derived lipids in tissue homeostasis and repair is poorly understood. Here, we identify an essential role for adipocyte lipolysis in regulating inflammation and repair after injury in skin. Genetic mouse studies revealed that dermal adipocytes are necessary to initiate inflammation aft...
Resistin-like molecule alpha (RELMα) and YM-1 are secreted proteins implicated in murine models of alternatively activated macrophage (AA/M2) accumulation and Th2-skewed inflammation. Since the gp130 cytokine Oncostatin M (OSM) induces a Th2-like cytokine and AA/M2 skewed inflammation in mouse lung, we here investigated regulation of RELMα and YM-1. Transient pulmonary overexpression of OSM by Adenovirus vector (AdOSM) markedly induced RELMα and YM-1 protein expression in total lung. In situ hyb...
Cellular plasticity is a transformation of a terminally differentiated cell into another cell type, which has been long known to occur in disease and regeneration. However, white adipocytes (fat cells) have only recently been observed to undergo different types of cellular plasticity. Adipocyte transdifferentiation into myofibroblasts and cancer-associated fibroblasts occurs in fibrosis and cancer, respectively. On the other hand, reversible adipocyte dedifferentiation into adipocyte progenitor ...
: Adipose tissues collectively as an endocrine organ and energy storage are crucial for systemic metabolic homeostasis. The major cell type in the adipose tissue, the adipocytes or fat cells, are remarkably plastic and can increase or decrease their size and number to adapt to changes in systemic or local metabolism. Changes in adipocyte size occur through hypertrophy or atrophy, and changes in cell numbers mainly involve de novo generation of new cells or death of existing cells. Recently, dedi...
Systemic sclerosis (SSc; scleroderma) is characterized by life-threatening progressive multiorgan fibrosis orchestrated by profibrotic myofibroblasts originating from different sources. Because recent data demonstrated that the majority of myofibroblasts in a murine scleroderma model arise from adipocytic progenitors through the adipocyte-myofibroblast transition process, we sought to determine whether the SSc microenvironment may affect the differentiation potential of adipose-derived stem cell...
#2Michal Rudnik(UZH: University of Zurich)H-Index: 2
Last. Oliver Distler(UZH: University of Zurich)H-Index: 98
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Systemic sclerosis (SSc) is an autoimmune fibrotic disease of unknown aetiology that is characterized by vascular changes in the skin and visceral organs. Autologous haematopoietic stem cell transplantation can improve skin and organ fibrosis in patients with progressive disease and a high risk of organ failure, indicating that cells originating in the bone marrow are important contributors to the pathogenesis of SSc. Animal studies also indicate a pivotal function of myeloid cells in the develo...