USP15 Maintains Transforming Growth Factor-β Pathway Activity by Deubiquitinating TGF-β Receptor I (TBR1) during Wound Healing.

08:00 EDT 10th April 2019 | BioPortfolio

Summary of "USP15 Maintains Transforming Growth Factor-β Pathway Activity by Deubiquitinating TGF-β Receptor I (TBR1) during Wound Healing."

Wound healing is a process of cutaneous barrier reconstruction that occurs after skin injury and involves diverse cytokines and cell types. Similar to several deubiquitinating enzymes, ubiquitin-specific peptidase 15 (USP15) can remove ubiquitin chains from specific proteins to rescue them from degradation. However, the regulatory role of USP15 in wound healing remains unclear. We investigated the dynamic function of USP15 in wound healing. First, in USP15 knockout mice, we observed a significant delay in wound closure. In addition, inhibition of cell proliferation and migration was observed in USP15-silenced human dermal fibroblasts. Through RNA sequencing, it was revealed that the transforming growth factor-β (TGF-β) pathway was suppressed after USP15 knockdown. Furthermore, co-immunoprecipitation (Co-IP) demonstrated that USP15 could interact with TGF-β receptor I (TBR1) and promote its deubiquitination, thereby maintaining TGF-β signalling pathway activity by enhancing TBR1 stability. These observations shed light on the function and mechanisms of USP15-mediated modulation of the TGF-β signalling pathway during wound healing, thus providing a novel potential target for the treatment of refractory wounds.


Journal Details

This article was published in the following journal.

Name: The American journal of pathology
ISSN: 1525-2191


DeepDyve research library

PubMed Articles [26200 Associated PubMed Articles listed on BioPortfolio]

The many talents of transforming growth factor-β in the kidney.

Preclinical data suggests that transforming growth factor-β (TGF-β) is arguably the most potent profibrotic growth factor in kidney injury. Despite this, recent clinical trials targeting TGF-β have...

Transforming growth factor-β signaling: Tumorigenesis and targeting for cancer therapy.

Transforming growth factor (TGF)-β is a multitasking cytokine such that its aberrant expression is related to cancer progression and metastasis. TGF-β is produced by a variety of cells within the t...

A Non-canonical Pathway with Potential for Safer Modulation of Transforming Growth Factor-β1 in Steroid-Resistant Airway Diseases.

Impaired therapeutic responses to anti-inflammatory glucocorticoids (GC) in chronic respiratory diseases are partly attributable to interleukins and transforming growth factor β1 (TGF-β1). However, ...

Impaired Autophagic Degradation of Transforming Growth Factor-β-Induced Protein by Macrophages in Lattice Corneal Dystrophy.

Lattice corneal dystrophy (LCD) is related to the denaturation of transforming growth factor-β-induced protein (TGFBIp). Autophagic degradation of the denatured proteins by macrophages is one pathway...

Loss of transforming growth factor-β1 in epithelium cells affects enamel formation in mice.

In order to understand the specific in vivo function of transforming growth factor-beta1 (TGF-β1), we successfully established aTGF-β1 deficient mouse model using a conditional knockout method. In t...

Clinical Trials [9534 Associated Clinical Trials listed on BioPortfolio]

Safety and Efficacy Study of GC1008 to Treat Renal Cell Carcinoma or Malignant Melanoma

The purpose of this study is to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of GC1008, a human anti-transforming growth factor-beta (TGFβ) monoclonal antibod...

Corneal Epitheliotropic Factors in Autologous Serum Eye Drops in Nonautoimmune and Stevens-Johnson Syndrome With Dry Eye

Autologous serum eye drops (ASE) have been becoming popular in treatment of severe dry eye for the past decade. One of the most beneficial properties of the ASE over artificial eye drops ...

Chitinases and Transforming Growth Factor Beta (TGFB) in Human Asthma

The purpose of this study is to find out the roles of two specific gene families (the chitinase gene family and the TGFB family). We hypothesize that chitinases and TGFb pathway genes will...

Community Awareness, Resources and Education (CARE II) Project: Project 1

The study hypothesis is that the increased incidence of cervical cancer observed in Appalachian women over their non-Appalachian counterparts is due in part to inherited and somatic altera...

Safety, Tolerability, and Pharmacokinetics of CAT-192 (Human Anti-TGF-Beta1 Monoclonal Antibody) in Patients With Early Stage Diffuse Systemic Sclerosis

Systemic Sclerosis (also known as Scleroderma) is a chronic, autoimmune disease of the connective tissue generally classified as one of the rheumatic diseases. Systemic Sclerosis causes f...

Medical and Biotech [MESH] Definitions

Cell-surface proteins that bind transforming growth factor beta and trigger changes influencing the behavior of cells. Two types of transforming growth factor receptors have been recognized. They differ in affinity for different members of the transforming growth factor beta family and in cellular mechanisms of action.

Hormonally active polypeptides that can induce the transformed phenotype when added to normal, non-transformed cells. They have been found in culture fluids from retrovirally transformed cells and in tumor-derived cells as well as in non-neoplastic sources. Their transforming activities are due to the simultaneous action of two otherwise unrelated factors, TRANSFORMING GROWTH FACTOR ALPHA and TRANSFORMING GROWTH FACTOR BETA.

A cell surface receptor involved in regulation of cell growth and differentiation. It is specific for EPIDERMAL GROWTH FACTOR and EGF related peptides including TRANSFORMING GROWTH FACTOR ALPHA, amphiregulin, and heparin-binding EGF-like growth factor. The binding of ligand to the receptor causes activation of its intrinsic tyrosine kinase activity and rapid internalization of the receptor-ligand complex into the cell.

A subtype of transforming growth factor beta that is synthesized by a wide variety of cells. It is synthesized as a precursor molecule that is cleaved to form mature TGF-beta 1 and TGF-beta1 latency-associated peptide. The association of the cleavage products results in the formation a latent protein which must be activated to bind its receptor. Defects in the gene that encodes TGF-beta1 are the cause of CAMURATI-ENGELMANN SYNDROME.

A 17-kDa single-chain polypeptide growth factor that plays a significant role in the process of WOUND HEALING and is a potent inducer of PHYSIOLOGIC ANGIOGENESIS. It binds to HEPARIN, which potentiates its biological activity and protects it from proteolysis. The growth factor is an extremely potent inducer of DNA synthesis in a variety of cell types from mesoderm and neuroectoderm lineages, and also has chemotactic and mitogenic activities. It was originally named acidic fibroblast growth factor based upon its chemical properties and to distinguish it from basic fibroblast growth factor (FIBROBLAST GROWTH FACTOR 2).

Quick Search


DeepDyve research library

Relevant Topics

Wound management
Anything that breaks the skin is a wound because when the skin is broken, there's a risk of germs getting into the body and causing an infection. Follow and track Wound Care News on BioPortfolio: Wound Car...

Complementary and Alternative Medicine
Alternative medicine are whole medical systems that did not fit with conventional medicine as they have completely different philosophies and ideas on the causes of disease, methods of diagnosis and approaches to treatment. Although often overlapping, co...

Acne Dermatology Eczema Psoriasis Wound Care Dermatology is the medical specialty concerned with the diagnosis and treatment of skin disorders (Oxford Medical Dictionary). As well as studying how the skin works, dermatology covers...

Searches Linking to this Article