Wei-Yang Gao

Vitamin D: a novel therapeutic approach for keloid, an in vitro analysis

Backgroundu2002 Vitamin D and its metabolites play an important role in calcium homeostasis, bone remodelling, hormone secretion, cell proliferation and differentiation. Recent studies also suggest a beneficial role of vitamin D in slowing the progression of tissue fibrosis. However, their effects on dermal fibrosis and keloids are unknown.

Troglitazone suppresses transforming growth factor-β1-induced collagen type I expression in keloid fibroblasts

Backgroundu2002 Peroxisome proliferator‐activated receptor (PPAR)‐γ agonists are increasingly used in patients with diabetes and some studies have suggested a beneficial effect on organ fibrosis. However their effects on dermal fibrosis in keloids are unknown.

Activation of peroxisome proliferator-activated receptor-γ inhibits transforming growth factor-β1 induction of connective tissue growth factor and extracellular matrix in hypertrophic scar fibroblasts in vitro

Peroxisome proliferator-activated receptor-γ (PPAR-γ) ligands have been recently reported to have beneficial effects on organ fibrosis. However, their effects on extracellular matrix (ECM) turnover in hypertrophic scar fibroblasts (HSFs), and the related molecular mechanisms are unknown. HSFs were cultured and exposed to different concentration PPAR-γ ligands in the presence of transforming growth factor-β1 (TGF-β1). In growth-arrested HSFs, a PPAR-γ natural ligand (15-deoxy-D12,14-prostaglandin J2, 15d-PGJ2) and a synthetic ligand (GW7845) dose-dependently attenuated TGFβ1-induced expression of Connective tissue growth factor (CTGF), collagens and fibronectin. Furthermore, the suppression of CTGF mRNA and protein expression are relieved by pretreatment with an antagonist of PPAR-γ (GW9662). Moreover, GW7845 and 15d-PGJ2 partially inhibited the expression and phosphorylation of the TGF-β1/Smad pathway. These results suggest that in TGFβ1-stimulated HSFs, PPAR-γ ligands caused an antiproliferative effect and reduced ECM production through mechanisms that included reducing CTGF expression, and a crosstalk between PPAR-γ and Smad may be involved in the inhibitory effects of PPAR-γ ligands.

Role of caveolin-1 in the pathogenesis of tissue fibrosis by keloid-derived fibroblasts in vitro.

Backgroundu2002 Recent studies have suggested that caveolin‐1 (cav‐1) plays an important role in the regulation of transforming growth factor (TGF)‐β1 signalling and participates in the pathogenesis of tissue fibrosis. However, its effects on dermal fibrosis keloids are unknown.

Peroxisome proliferator-activated receptor-γ (PPAR-γ) agonist inhibits transforming growth factor-beta1 and matrix production in human dermal fibroblasts

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists are increasingly used in patients with diabetes, and some studies have suggested a beneficial effect on organ fibrosis, but their effects on dermal cell growth and extracellular matrix (ECM) turnover are unknown. To investigate the effect of the PPAR-gamma agonist troglitazone on cell growth and matrix production in human dermal fibroblasts (HDF), HDF were cultured and grown in a different concentration of troglitazone. PPAR-gamma expression and matrix production were measured in HDF in the presence of troglitazone. The mRNA expressions of TGF-beta1, collagen I (Col I) and fibronectin (FN) were determined by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). The protein of transforming growth factor-beta1 (TGF-beta1) was determined by enzyme-linked immunosorbent assay (ELISA) and proteins of Col I and FN were determined by Western blotting. The mRNA expression of TGF-beta1, Col I and FN were significantly decreased in HDF in 15-30 micromol l(-1) troglitazone compared to the control group with Dulbeccos modified Eagles medium (P<0.01). An obvious decrease of TGF-beta1 protein was found in troglitazone-treated groups as compared to the control group (P<0.05). Exposure of HDF to troglitazone reduced col I secretion (P<0.05), and fibronectin secretion (P<0.05). This study suggests that PPAR-gamma agonist will provide a novel approach with therapeutic potential in dermal fibrosis, such as hypertrophic scar, keloid and so on.

NADPH oxidase-2 is a key regulator of human dermal fibroblasts: a potential therapeutic strategy for the treatment of skin fibrosis

The proliferation of human skin dermal fibroblasts (HDFs) is a critical step in skin fibrosis, and transforming growth factor‐beta1 (TGF‐β1) exerts pro‐oxidant and fibrogenic effects on HDFs. In addition, the oxidative stress system has been implicated in the pathogenesis of skin disease. However, the role of NADPH oxidase as a mediator of TGF‐β1‐induced effects in HDFs remains unknown. Thus, our aim was to investigate the role of NADPH in human skin dermal fibroblasts. Primary fibroblasts were cultured and pretreated with various stimulants. Real‐time Q‐PCR and Western blotting analyses were used for mRNA and protein detection. In addition, siRNA technology was applied for gene knock‐down analysis. Hydrogen peroxide production and 2′,7′‐dichlorofluorescein diacetate (DCFDA) measurement assay were performed. Here, our findings demonstrated that HDFs express key components of non‐phagocytic NADPH oxidase mRNA. TGF‐β1 induced NOX2 and reactive oxygen species formation via NADPH oxidase activity. In contrast, NOX3 was barely detectable, and other NOXs did not display significant changes. In addition, TGF‐β1 phosphorylated MAPKs and increased activator protein‐1 (AP‐1) in a redox‐sensitive manner, and NOX2 suppression inhibited baseline and TGF‐β1‐mediated stimulation of Smad2 phosphorylation. Moreover, TGF‐β1 stimulated cell proliferation, migration, collagen I and fibronectin expression, and bFGF and PAI‐1 secretion: these effects were attenuated by diphenylene iodonium (DPI), an NADPH oxidase inhibitor, and NOX2 siRNA. Importantly, NOX2 siRNA suppresses collagen production in primary keloid dermal fibroblasts. These findings provide the proof of concept for NADPH oxidase as a potential target for the treatment of skin fibrosis.

The free dorsoradial forearm perforator flap: anatomical study and clinical application in finger reconstruction.

The perforator flaps are characterized by their thinness and the adjustable length of their vascular pedicle. The purpose of this investigation is to refine the anatomy of the perforators in the middorsoradial forearm and present our clinical experience using this free perforator flap in the reconstruction of finger defects. Anatomic study was conducted on 46 cadaver forearms. It was noted that a perforator was consistently observed in the midforearm exhibiting 4 patterns, in which a dorsoradial perforator was present with 37 cases (80.4%) originating from the interosseous artery system (patterns 1–3) and 9 cases (19.6%) from the descending branch of the radial recurrent artery (pattern 4). This perforator consistently emerged in the intermuscular septum between the extensor carpi radialis longus and extensor digitorum communis. Twenty free flaps based on this middorsoradial cutaneous perforator were elevated for the coverage of soft tissue defects of fingers (range: 3 cm × 2.0 cm to 5 cm × 2.5 cm) in 17 patients. All the flaps survived with satisfactory outcomes. Clinical findings on this perforator in terms of its origins and courses coincided with the anatomic results (&khgr;2 = 0.287, P = 0.962). The free flap based on this perforator is a reliable perforator flap in spite of varied origins.

A novel regulatory function for miR-29a in keloid fibrogenesis

A growing body of evidence has shown that microRNA‐29 (miR‐29) plays a central role in the progression of fibrosis. However, the mechanisms underlying the role of miR‐29 in keloid fibrogenesis remain unknown.

Dorsal Pentagonal Local Flap: A New Technique of Web Reconstruction for Syndactyly Without Skin Graft

BackgroundMany techniques for web space reconstruction have been described over the years. However, few techniques are completely satisfactory in terms of cosmetic requirement and functional recovery due to scar contracture, web creep, or conspicuous scarring resulting from skin grafting or additional incisions on the dorsal palm. Based on the anatomy of the dorsal metacarpal artery, the authors describe a local pentagonal advancement flap including perforators of the dorsal metacarpal artery to optimize web reconstruction and facilitate direct closure in the syndactyly treatment.MethodsA local dorsal pentagonal advancement flap was used to reconstruct 17 web spaces in ten patients. The skin of the syndactylized fingers was brought to the web space from the dorsum of the two adjacent syndactylized fingers to cover the web area, facilitating a skin graft-free procedure for web reconstruction.ResultsAll 17 web releases were successfully reconstructed. During the follow-up period of 23–35xa0months, the appearance of all the reconstructed webs was similar to that of the adjacent normal webs, and all the patients had full functional recovery. No case of web creep was reported during this period, and none of the patients required a secondary operation.ConclusionThe dorsal pentagonal advancement flap is a dependable flap based on known perforators from the dorsal metacarpal arteries. The reported technique is a simple and effective technique for the correction of simple syndactyly and is especially suitable for reconstruction of two webs in multiple syndactyly simultaneously, avoiding the need for skin grafts and leaving acceptable scars on the dorsum of the hand for web reconstruction.

Hand reconstruction with lobulated combined flaps based on the circumflex scapular pedicle

Repair of multiple soft tissue defects on hand often pose a difficult problem to the reconstructive surgeons with employing a limited number of reliable flaps and recipient vessels. This report is to explore the feasibility and advantage of the treatment of multiple soft tissue defects on hand with combined island flaps based on branches of the circumflex scapular system. From 2002 to 2006, nine patients had transfer of the scapular lobulated combined flaps based on the transverse branch, ascending branch, and descending branch of the circumflex scapular vascular pedicle for coverage of soft‐tissue defects over injured hands. Follow‐up ranged from 6 months to 24 months with average 12.1 months all of nine flaps completely survived without complications. Arterial insufficiency was found in one flap because of the pedicle compression in the subcutaneous tunnel. The blood supply to flap was restored after the compression was released. All transferred flaps showed good appearance without significantly swelling and congestion. Two flaps underwent secondary debulking surgery. At 6 months postoperatively, partial protective sensation (S1) was restored in the flaps. The donor sites were directly closed in six cases. Skin grafts were used to cover the donor sites in other three cases. All of donor sites healed without complications. Our report shows that the management of multiple soft tissue defects on hand in complex hand injuries with lobulated flaps of circumflex scapular system can obtain good results for its good appearance and low donor site complications. It is probably the optimal surgical intervention for these injuries.