TDP-43 regulates cholesterol biosynthesis by inhibiting sterol regulatory element-binding protein 2.

Dyslipidemia is considered an essential component of the pathological process of amyotrophic lateral sclerosis (ALS), a fatal motor neuron disease. Although TAR DNA Binding Protein 43 kDa (TDP-43) links both familial and sporadic forms of ALS and cytoplasmic aggregates are a hallmark of most cases of ALS, the molecular mechanism and the in vivo relation of ALS dyslipidemia with TDP-43 have been unclear. To analyze the dyslipidemia-related gene expression by TDP-43, we performed expression microarray and RNA deep sequencing (RNA-Seq) using cell lines expressing high levels of TDP-43 and identified 434 significantly altered genes including sterol regulatory element-binding protein 2 (SREBP2), a master regulator of cholesterol homeostasis and its downstream genes.

Chondroitin Sulfate Promotes the Proliferation of Keloid Fibroblasts Through Activation of the Integrin and Protein Kinase B Pathways.

Keloids are dermal fibroproliferative tumors that arise beyond the boundary of the original wound edges and invades adjacent tissue. Keloids are characterized by the extensive production of extracellular matrix (ECM) and abnormal fibroblast proliferation. Chondroitin sulfate (CS) is one of the major structural components of cartilage and ECM.

is a therapeutic target in SPG4-related hereditary spastic paraplegia human neurons.

Recent reports, including ours, have indicated that microRNA (miR)-33 located within the intron of sterol regulatory element binding protein (SREBP) 2 controls cholesterol homeostasis and can be a potential therapeutic target for the treatment of atherosclerosis. Here, we show that , which encodes a microtubule-severing protein called SPASTIN, was a novel target gene of in human. Actually, the miR-33 binding site in the 3'-UTR is conserved not in mice but in mid to large mammals, and it is impossible to clarify the role of on in mice.

HtrA1 Is Specifically Up-Regulated in Active Keloid Lesions and Stimulates Keloid Development.

Keloids occur after failure of the wound healing process; inflammation persists, and various treatments are ineffective. Keloid pathogenesis is still unclear. We have previously analysed the gene expression profiles in keloid tissue and found that HtrA1 was markedly up-regulated in the keloid lesions.

β-Adrenergic Receptor Blockers Reduce the Occurrence of Keloids and Hypertrophic Scars after Cardiac Device Implantation: A Single-Institution Case-Control Study.

Background: Keloids and hypertrophic scars are characterized by excessive proliferation of fibroblasts; abnormal accumulation of extracellular matrix; and clinical findings of raised, red, itchy, and painful lesions. There are few sufficient interventions for keloids, and the development of new therapeutic agents is urgently needed. Several studies suggest that a therapeutic possibility is β-adrenergic receptor blocker treatment.

Regeneration of elastic fibers by three-dimensional culture on a collagen scaffold and the addition of latent TGF-β binding protein 4 to improve elastic matrix deposition.

The objective of this study was to investigate the effects of latent TGF-β binding protein 4 (LTBP-4) on elastic fiber regeneration in three-dimensional cultures of human dermal fibroblasts (HDFs). Appropriate collagen scaffold for elastic fiber regeneration was also examined. Collagen sponges cross-linked at 120 °C and composed of small pores (25 μm on average) was favorable for elastic fiber regeneration by HDFs.

The Shear Wave Velocity on Elastography Correlates with the Clinical Symptoms and Histopathological Features of Keloids.

Background: Keloids present as red, painful lesions causing serious functional and cosmetic problems; however, there is no consensus regarding tools for objectively evaluating keloids. To demonstrate the utility of shear wave elastography in keloids, we investigated the correlations between clinical symptoms, ultrasound shear wave velocity, and histopathological findings.

Methods: Three patients with keloids containing both red hypertrophic and mature areas were evaluated using the shear wave velocity and histopathological findings.

Severe Acute Radiodermatitis in a Keloid Patient with Takayasu's Arteritis.

Although combination therapy for keloid including postoperative radiation therapy (RT) is common, the radiation toxicity of RT in a patient with a history of collagen vascular disease has not been fully recognized. We experienced a case of an acute radiodermatitis in a patient with keloid. This patient had a chest keloid because of the bypass surgery for Takayasu's arteritis.

A toe keloid after syndactyly release treated with surgical excision and intralesional steroid injection.

A keloid is a benign fibroproliferative disease of unknown etiology. Although it is common among Asians, the development of keloid on the foot is rare. We experienced a case of a keloid which arose on the foot of a 4-year-old boy after the surgical release of syndactyly.

Treatment for infection of artificial dura mater using free fascia lata.

Synthetic artificial dura mater materials, such as expanded polytetrafluoroethylene sheets, are widely used in dura mater reconstruction in cases involving brain tumors or trauma surgery. In patients with postoperative infection related to the use of artificial dura mater, surgical debridement of the infected wound and removal of the artificial dura mater materials are necessary to control infection. In cases involving cerebrospinal fluid leakage, dura mater reconstruction must be performed immediately.

Response to comment on "Drug screening for ALS using patient-specific induced pluripotent stem cells".

Our work and the study of Bilican et al. highlight the need for complementary assays to detect subtle phenotypic differences between control and mutant induced pluripotent stem cell lines.

Chondroitinase injection improves keloid pathology by reorganizing the extracellular matrix with regenerated elastic fibers.

Keloids are a proliferative fibrotic disease characterized by abnormal accumulation of extracellular matrix in the dermis. Keloid lesions lack skin plasticity due to deficiencies in elastic fiber formation in the extracellular matrix. The loss of elastic fiber is caused by excessive accumulation of chondroitin sulfate (CS), a sulfated glycosaminoglycan.

Modeling Alzheimer's disease with iPSCs reveals stress phenotypes associated with intracellular Aβ and differential drug responsiveness.

Oligomeric forms of amyloid-β peptide (Aβ) are thought to play a pivotal role in the pathogenesis of Alzheimer's disease (AD), but the mechanism involved is still unclear. Here, we generated induced pluripotent stem cells (iPSCs) from familial and sporadic AD patients and differentiated them into neural cells. Aβ oligomers accumulated in iPSC-derived neurons and astrocytes in cells from patients with a familial amyloid precursor protein (APP)-E693Δ mutation and sporadic AD, leading to endoplasmic reticulum (ER) and oxidative stress.

Latent TGF-β binding protein 4 promotes elastic fiber assembly by interacting with fibulin-5.

Elastic fiber assembly requires deposition of elastin monomers onto microfibrils, the mechanism of which is incompletely understood. Here we show that latent TGF-β binding protein 4 (LTBP-4) potentiates formation of elastic fibers through interacting with fibulin-5, a tropoelastin-binding protein necessary for elastogenesis. Decreased expression of LTBP-4 in human dermal fibroblast cells by siRNA treatment abolished the linear deposition of fibulin-5 and tropoelastin on microfibrils.

Multipotent stem cells are effectively collected from adult human cheek skin.

Skin-derived precursor (SKP) cells are a valuable resource for tissue engineering and regenerative medicine, because they represent multipotent stem cells that differentiate into neural and mesodermal progenies. Previous studies suggest that the stem cell pool decreases with age. Here, we show that human multipotent SKP cells can be efficiently collected from adult cheek/chin skin, even in aged individuals of 70-78years.

An ex vivo model employing keloid-derived cell-seeded collagen sponges for therapy development.

The most distinctive feature of keloid is the extreme deposition of extracellular matrix, including collagens and proteoglycans (PGs). The focus of this study was the PG versican, which presumably defines keloid volume because of its ability to retain large amounts of water through its component glycosaminoglycans (GAGs). The excessive deposition of versican in keloids was examined by immunohistochemical analysis and by upregulation of the versican gene in these lesions by real-time PCR.

Drug screening for ALS using patient-specific induced pluripotent stem cells.

Amyotrophic lateral sclerosis (ALS) is a late-onset, fatal disorder in which the motor neurons degenerate. The discovery of new drugs for treating ALS has been hampered by a lack of access to motor neurons from ALS patients and appropriate disease models. We generate motor neurons from induced pluripotent stem cells (iPSCs) from familial ALS patients, who carry mutations in Tar DNA binding protein-43 (TDP-43).

Keloids can be forced into remission with surgical excision and radiation, followed by adjuvant therapy.

We have treated keloids using a combination of surgical excision and postoperative irradiation. The objective of this study was to evaluate the results of our treatment over 12 years. From 1995 until 2006, we treated keloids using the aforementioned treatment.

Adipose tissue-specific regulation of angiotensinogen in obese humans and mice: impact of nutritional status and adipocyte hypertrophy.

Background: The adipose tissue renin-angiotensin system (RAS) has been implicated in the pathophysiology of obesity and dysfunction of adipose tissue. However, neither regulation of angiotensinogen (AGT) expression in adipose tissue nor secretion of adipose tissue-derived AGT has been fully elucidated in humans.

Methods: Human subcutaneous abdominal adipose tissue (SAT) biopsies were performed for 46 subjects with a wide range of body mass index (BMI).

Elastic fiber assembly is disrupted by excessive accumulation of chondroitin sulfate in the human dermal fibrotic disease, keloid.

Keloid is a fibrotic disease characterized by abnormal accumulation of extracellular matrix in the dermis. The keloid matrix contains excess collagen and glycosaminoglycans (GAGs), but lacks elastic fiber. However, the roles of these matrix components in the pathogenesis of keloid are largely unknown.

[Clinical regenerative medicine: the skin].

Tissue engineering of skin is classified into acellular artificial skin and cellular artificial skin. Acellular artificial skin or artificial dermis, is composed of an inner collagen sponge and an outer silicone film. When placed on wounds, the collagen sponge is spontaneously converted into a dermis-like connective tissue.

ARMET is a soluble ER protein induced by the unfolded protein response via ERSE-II element.

Arginine rich, mutated in early stage of tumors (ARMET) was first identified as a human gene highly mutated in a variety of cancers. However, little is known about the characteristics of the ARMET protein and its expression. We identified ARMET as a gene upregulated by endoplasmic reticulum (ER) stress.

Identification of cartilage progenitor cells in the adult ear perichondrium: utilization for cartilage reconstruction.

For cartilage reconstruction, it is still difficult to obtain a sufficient volume of cartilage and to maintain its functional phenotype for a long period. Utilizing tissue stem cells is one approach to overcome such difficulties. We show here the presence of cartilage progenitor cells in the ear perichondrium of adult rabbits by 5-bromo-2'-deoxyuridine labeling, clonogenicity, and differentiation analyses.