The endoplasmic reticulum–resident collagen chaperone Hsp47 interacts with and promotes the secretion of decorin, fibromodulin, and lumican

Ishikawa, Yoshihiro; Rubin, Kristofer; Bächinger, Hans Peter; Kalamajski, Sebastian

doi:10.1074/jbc.ra117.000758

Cited by 23 publications

(20 citation statements)

References 45 publications

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“…Nascent α chains by different genes are encoded first to compose the N-terminus. The next step of assembly into a three-helix structure begins with the C-terminus of the nascent α chains to form procollagen, which is accompanied by certain chaperone proteins including heat shock protein 47, prolyl-hydroxylase, and protein disulfide isomerase to ensure precise alignment [9]. Hydroxylation and glycosylation in the endoplasmic reticulum are two main modifications that occur after translation, and the hydroxylation modification is regulated by vitamin C and pyruvate metabolism [10,11].…”

Section: Physiological and Physicochemical Properties Of Collagenmentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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Section: Physiological and Physicochemical Properties Of Collagenmentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…This gene encodes the heat inducible protein HSP47, which is a member of the serpine family of proteinase inhibitors. HSP47 is crucial during pro-collagen biosynthesis and plays and important role in the secretion of decorin, fibromodulin and lumican for the assembly of the extracellular matrix 82 . In primary grade IV gioblastoma multiforme (GBM) primary cells, an over-expression of HSP47 promoted the expression of extracellular matrix (ECM)-related genes such as COL4A2 and MMP9 83 .…”

Section: Serpinh1mentioning

confidence: 99%

Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration

Gómez-Acevedo

Dai²,

Strub

et al. 2020

Sci Rep

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Infantile hemangiomas (IHs) are the most common benign tumors in early childhood. They show a distinctive mechanism of tumor growth in which a rapid proliferative phase is followed by a regression phase (involution). Propranolol is an approved treatment for IHs, but its mechanism of action remains unclear. We integrated and harmonized microRNA and mRNA transcriptome data from newly generated microarray data on IHs with publicly available data on toxicological transcriptomics from propranolol exposure, and with microRNA data from IHs and propranolol exposure. We identified subsets of putative biomarkers for proliferation and involution as well as a small set of putative biomarkers for propranolol's mechanism of action for IHs, namely EPAS1, LASP1, SLC25A23, MYO1B, and ALDH1A1. Based on our integrative data approach and confirmatory experiments, we concluded that hypoxia in IHs is regulated by EPAS1 (HIF-2α) instead of HIF-1α, and also that propranolol-induced apoptosis in endothelial cells may occur via mitochondrial stress. Infantile hemangiomas (IHs) are the most common benign tumor of the vascular endothelium in infants and are present in 4 to 10% of children younger than 12 months 1,2. They manifest in any part of the body but around 60% of the cases arise in the head and neck 3. IHs have a unique growth pattern that is divided into three phases: proliferation, quiescence and involution 4. Despite the fact that the majority of IHs involute completely by 7 years of age, their hyper-proliferation can cause significant functional and disfiguring consequences and morbidities such as ulceration, bleeding, and pain. It is estimated that up to 40% of the lesions will require either surgical or medical intervention 3,5. Histologically, IHs in the proliferative phase show a lack of organization of blood vessels with densely packed capillaries composed of immature endothelial cells surrounded by pericytes, whereas during involution the capillaries are replaced with fatty and fibrous tissue 6. These findings suggest that the proliferation phase is orchestrated by angiogenesis or growth factors that lead to high mitotic rates. Among such markers reported in the literature are vascular endothelial growth factor A (VEGF-A) 7 , basic fibroblast growth factor (bFGF), proliferating cell nuclear antigen (PCNA), type IV collagenase 8 , and insulin-like growth factor 2 (IGF-2) 9. On the other hand, during the involution phase there is a high expression of antiangiogenic factors (e.g., tissue inhibitor of metalloproteinase TIMP1) 8 and increasing apoptosis of endothelial cells 10. However, high expression of growth factors in both the proliferating and involution phases (e.g. bFGF) makes it difficult to clearly identify causative factors for IHs' development. From the clinical perspective, it is important to find biomarkers that robustly differentiate between proliferation and involution phases on IHs, with the hope that those biomarkers will guide medical decisions towards optimal treatments. Propranolol is a non-selective β-adre...

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“…The present results reveal that a 24-hour stimulation with the modulated signal induced significant overexpression of DCNcore, but not of mature decorin, which could be due to the fact that the stimulus was applied at an early stage, prior to formation of the mature protein. On the other hand, it has been reported that the Hsp47 protein residing in the endoplasmic reticulum binds decorin with an affinity comparable to that of the interaction between Hsp47 and type I collagen, and that the lack of Hsp47 inhibits both the secretion of collagen and that of the SLRPs lumican and decorin (Ishikawa et al 2018). This inkling that besides playing a role in collagen folding and secretion (Ishida et al 2006;Ishikawa et al 2016;Nagai et al 2000) Hsp47 can intervene in SLRP secretion, contributes to better understanding the coordinated molecular interactions that control the secretion and organization of the functional collagen matrix.…”

Section: Discussionmentioning

confidence: 99%

Effects of the signal modulation on the response of human fibroblasts to in vitro stimulation with subthermal RF currents

Trillo

Martínez

Úbeda

2020

Electromagnetic Biology and Medicine

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Capacitive-Resistive Electric Transfer (CRET) thermotherapies aim at tissue repair and regeneration through non-invasive application of RF currents. We have reported that the cellular response to subthermal CRET currents is non-linearly dependent on the signal frequency, and that in vitro exposure to a 448-kHz CRET signal promotes ADSC proliferation, as well as collagen and glycosaminoglycan synthesis in prechondrocytic cells. The present work investigates the response of neonatal fibroblasts to subthermal exposure (100 µA/mm 2) to two CRET signals: a 448-kHz, nonmodulated sinusoidal wave vs. a 20-kHz amplitude-modulation of the 448-kHz carrier. To that end, cell proliferation and expression of the biomarkers Hsp47, Hsp27 and decorin were assessed by cell count, PCNA and Western blotting. The results revealed that while both signals significantly and equivalently increased early (4 h) expression of Hsp47, the modulated signal was more efficient in inducing Hsp27 and decorin overexpression and promoting cell proliferation. These data indicate that the cellular response is dependent on the RF signal modulation and suggest that the therapeutic effects of CRET could be mediated by promotion of fibroblastic proliferation and overexpression of biomarkers that are essential in skin regeneration.

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The endoplasmic reticulum–resident collagen chaperone Hsp47 interacts with and promotes the secretion of decorin, fibromodulin, and lumican

Cited by 23 publications

References 45 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

Identification of putative biomarkers for Infantile Hemangiomas and Propranolol treatment via data integration

Effects of the signal modulation on the response of human fibroblasts to in vitro stimulation with subthermal RF currents

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