대퇴골두괴사 모델에서 COMP-Angiopoietin-1의 효과 : Effect of COMP-Angiopoietin-1 on Ischemic Necrosis of the Femoral Head in Rats

윤선중 전북대학교 대학원 2014 국내박사

Ischemic necrosis of the femoral head (INFH) can lead to loss of femoral head architecture and deformity. Moreover, the process of bone healing is intimately associated with angiogenesis. We considered that COMP-Angiopoietin-1 (COMP-Ang1, an angiogenic factor) might preserve femoral head structure and facilitate bone repair. COMP-Ang1 facilitated necrotic femoral head repair via the enhancement of angiogenesis. Moreover, bone morphogenic protein-2 (BMP-2) has been shown to stimulate osteoblast recruitment and new bone formation under condition of fracture-healing and spinal fusion. Combined therapy consisting of BMP-2 and COMP-Ang1 can potentiate therapeutic effect of BMP-2 on a rat model of ischemic necrosis of the femoral head (INFH). INFH was surgically induced in the femoral head of rats. Two weeks later, COMP-Ang1 was injected directly into infarcted areas. One set of the rats were divided into the following groups; 1) the sham-operated group (the sham group), 2) the bovine serum albumin-injected group (the BSA group), and 3) the COMP-Ang1-injected group (the COMP-Ang1 group) (n = 20/group). Another set of the rats were dived into the following groups; 1) the sham group), 2) the BSA group, 3) the BMP-2 group, and 4) the BMP-2 + COMP-Ang1 group (n=20/group). Radiological, histological and histomorphometric assessments were performed. Blood and tissue levels of transforming growth factor-beta (TGF-β) were determined by ELSIA. Effect of COMP-Ang1 on BMP-2 signaling was analyzed by Western blotting. In the first set of experiment, radiographs showed better preservation of femoral head architecture in the COMP-Ang1 group than in the BSA group. Histological finding and immunostaining of endothelial cells for factor VIII revealed that COMP-Ang1 group animals showed higher levels of vascularity in the secondary ossification center of infarcted femoral heads. In the second set of experiment, radiographs showed better preservation of femoral head architecture in the BMP-2 + COMP-Ang1 group than in the BSA or BMP-2 group. Histological finding showed an increased trabecular bone in the BMP-2 + COMP-Ang1 group. Immunostaining of endothelial cells for factor VIII revealed that BMP-2 + COMP-Ang1 group animals showed higher levels of vascularity in infarcted femoral heads. In addition, COMP-Ang1 treatment decreased TGF-β effects in the INFH. COMP-Ang1 also increased activities of differentiation effect of BMP-2 in infarcted femoral head. These results suggest that COMP-Ang1 enhanced preservation of necrotic femoral head through potentiating BMP-2 signaling pathways and angiogenesis. Combination of BMP-2 and COMP-Ang1 could be clinically useful for therapeutic application to INFH.

신장 허혈성 재관류 손상에서 COMP-Ang1의 보호효과

정유진 전북대학교 대학원 2008 국내석사

Acute kidney injury, characterized by rapid decline in glomerular filtration rate, is a major cause of morbidity and mortality. Renal ischemia reperfusion injury is the leading cause of acute kidney injury and this injury induces a cascade of events leading to cellular damage. Microvascular endothelial cell injury induces loss of renal endothelial function such as regulation of vascular tone, tissue perfusion, permeability, and inflammation. Endothelial dysfunction has detrimental effect upon renal function in ischemic acute kidney injury. A modality to improve endothelial dysfunction in ischemia reperfusion injured kidney can be a good therapeutic approach in renal IRI. Recently, COMP-Angiopoietin(Ang)1, a variant of native Ang1 was developed. However, there is no report about effect of COMP-Ang1 in renal ischemia reperfusion injury. In this study, I investigated the endothelial protective effect of COMP-Ang1 in renal ischemia reperfusion injury. I evaluated the tubular injury score after treatment with COMP-Ang1 or LacZ adenovirus in renal ischemia reperfusion injury model in mice. COMP-Ang1 significantly decreased renal IRI-induced tubular damage and improved blood urea nitrogen and serum creatinine. COMP-Ang1 prevented the renal ischemia reperfusion injury-induced decrease of renal blood flow and increased renal vascular permeability, renal vascular resistance. COMP-Ang1 also mitigated the effects of ischemia reperfusion injury on the number of F4/80 positive macrophage infiltrating, monocyte chemoattractant protein-1 expression and increased the number of Ki67 and platelet endothelial cell adhesion molecule-1 positive cells. These finding indicated that COMP-Ang1 may protect against endothelial dysfunction by renal ischemia reperfusion injury. 급성 신 손상은 사구체 여과율의 저하를 특징으로 하는 환자의 사망에 주된 이유이다. 허혈성 재관류 신 손상은 급성 신 손상을 일으켜 세포손상을 야기한다. 미세혈관 내피세포 손상은 혈관상태, 조직 내 관류, 투과성, 염증반응과 같은 신장 내피세포기능 저하를 유도한다. 허혈성 급성 신 손상에서 내피세포 기능 장애는 신장 기능을 저해한다. 이런, 내피세포 기능 장애의 개선은 허혈성 재관류 신 손상 치료에 한 발 다가설 수 있을 것이다. COMP-Angiopoietin (Ang)1은 기존 Ang1의 변형 물질로 허혈성 재관류 신 손상에서의 효과에 대한 보고가 없다. 본 실험은 허혈성 재관류 신 손상에서 COMP-Ang1의 신장 보호효과에 대한 실험을 시행하였다. 백서에 COMP-Ang1과 LacZ adenovirus를 각각 투여한 후 허혈성 재관류 신 손상 모델을 만들어 신 손상의 정도를 측정하였다. COMP-Ang1은 허혈성 재관류 신손상에 의한 세뇨관 손상을 의의있게 감소시켰고 혈액 내 요소질소와 혈청 크레아티닌을 개선시켰다. 또한, 허혈성 재관류 신손상에 의한 신혈류의 감소, 신장 혈관의 투과성 증가와 신장 혈관 저항을 보호하였다. COMP-Ang1은 허혈성 재관류 신손상에서 F4/80 양성 대식세포의 신장 간질내로의 침윤과 monocyte chemoattractant protein-1 단백질의 발현을 조절하였고, Ki67과 platelet endothelial cell adhesion molecule-1 양성인 세포수도 증가시켰다. 결론적으로 COMP-Ang1은 허혈성 재관류 신손상에 의한 내피세포 기능장애를 조절함으로써 허혈성 재관류 신손상을 보호하는 역할을 한다.

Effects of COMP-Ang1 on Survivals of Mouse Bone Marrow Derived Mesenchymal Cells

서민철 전남대학교 대학원 2009 국내박사

The potential influences of mesenchymal stem cell (MSC)-based therapies in bone tissue engineering are numerous. However, clinical uses of the MSCs are still limited because transplanted cells frequently undergo apoptosis due to lack of vascular system. The angiopoietin-1(Ang1)/Tie-2 signaling pathways play an important role in vessel formation and survival of endothelial cells, neurons, cardiomyocytes and MSCs. This study was to investigate the effect of COMP-Ang1, a soluble and stable Ang1 variant with short coiled-coil domain of cartilage oligomeric matrix protein (COMP), on survivals of mouse bone marrow derived mesenchymal cells under nutrient-deprived condition. Multipotent murine mesenchymal cells, C3H10T1/2, were cultured with Ang1 and COMP-Ang1 under nutrient-deprivation in the presence or absence of phosphatidylinositol 3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) inhibitor. Cell viability test was done using EZ cytox assay kit, and the phosphorylation of Akt, p38, and ERK was detected by Western blot analysis. Changes of a cell cycle-dependent gene and pro-apoptotic factor are analyzed by RT-PCR and Western blot. Results revealed that C3H10T1/2 mesenchymal cell lines express both Tie2 receptor and Ang-1. Recombinant Ang1 and COMP-Ang1 increased survivals of nutrient-deprived C3H10T1/2 in a dose-related fashion, and it was inhibited by inhibitors of PI3K (LY294002) and ERK (PD098059). In addition, Ang1 and COMP-Ang1 stimulated the phosphorylation of Akt, p38 and ERK, and it was also inhibited by LY294002, PD098059, and p38 MAPK inhibitor (SB203580). Nutrient-deprivation leaded to decreases in cyclin D1 mRNA expression, a positive regulator of cell cycle, and increases in the pro-apoptotic caspase-3 expression. Ang1 and COMP-Ang1 recovered the nutrient-deprived cyclin D1 and caspase-3 expression to control levels. Effectiveness of COMP-Ang1 on survivals of the mesenchymal cells did not differ statistically from that of native form of Ang1. These results suggest that COMP-Ang1 has a protective role in survivals of nutrient-deprived mesenchymal cell through MAPK and PI3K/Akt pathways, and that COMP-Ang1 may be used as a survival factor for mesenchymal cell-based tissue engineering.

혈관신생촉진인자 COMP-Ang1의 항파골세포, 항염증반응 및 골분화 활성 효과 및 기전에 관한 연구

백영현 전북대학교 일반대학원 2019 국내박사

COMP-Ang1, a chimera of angiopoietin-1 (Ang1) and a short coiled-coil domain of cartilage oligomeric matrix protein (COMP), has been considered as a therapeutic agent enhancing tissue regeneration with increased angiogenesis, as well as inducing the homing of stem cells. However, the nature of COMP-Ang1 in inhibiting inflammatory responses, stimulating osteoclastic or osteoblastic differentiation, and inducing migration of stem-like cells are not completely understood. The therapeutic efficacy of COMP-Ang1 to suppress inflammatory periodontium damage and the related mechanisms are not also entirely elucidated. This study initially investigated how COMP-Ang1 affects lipopolysaccharide (LPS)-induced osteoclastic differentiation of RAW 264.7 macrophages. The addition of COMP-Ang1 decreased significantly osteoclast differentiation and activation in the cells and this decrease was almost completely restored by combined treatment with 25 μM LY294002, a pharmacological phosphatidylinositol 3-kinase (PI3K) inhibitor. COMP-Ang1 also blocked the expression of inflammation-related molecules, such as cyclooxygenase 2 (COX-2), intercellular adhesion molecule 1 (ICAM-1), and interleukin-8 (IL-8) in LPS-stimulated human periodontal ligament fibroblasts (hPLFs). In addition, the COMP-Ang1 enhanced differentiation of hPLFs into osteoblasts along with increased alkaline phosphatase (ALP) activity and intracellular calcium accumulation. Additional experiments revealed that COMP-Ang1-mediated osteoblastogenesis was correlated with the increased expression of bone-specific markers including runt-related transcription factor 2, osterix, bone morphogenetic protein 2, bone sialoprotein, osteoclacin, osteopontin, type I collagen, and ALP, as well as activator protein-1 subfamily and Tie2. The addition of COMP-Ang1 induced in vitro migration of bone marrow-mesenchymal stem cells (BMMSCs) and this migration was significantly suppressed by Tie2 knockdown and by supplementation with CXCR4-specific peptide antagonist (AMD3100) or PI3K inhibitor (LY294002), but not with p-p38 mitogen-activated protein kinase inhibitor (SB203580). Otherwise, this study also explored whether a local delivery of COMP-Ang1 protects LPS/ligature-induced periodontal destruction in rats. As the results, μCT and histological analyses exhibited that COMP-Ang1 inhibits LPS-mediated degradation of periodontal tissues and suppresses osteoclast number and the expression of osteoclast-specific and inflammation-related molecules (cathepsin-K, matrix metalloproteinase 9, COX-2, IL-8, tumor necrosis factor-α, and ICAM-1) in the inflamed region of periodontitis rats. Collectively, the current findings confirm that COMP-Ang1 contains a therapeutic potential capable of preventing inflammatory periodontal damages, as well as stimulating bone healing process via its potentials able to inhibit osteoclastic activation and inflammatory response along with its stimulating capacity for osteogenic differentiation and migration of progenitor cells or stem-like cells.

COMP-Ang1 기반 골재생 및 조골세포분화 유도 연구

임신생 전북대학교 일반대학원 2013 국내박사

Bone development and fracture repair include the coordination of multiple events such as migration, differentiation, and activation of multiple cell types and tissues. Angiogenesis plays a critical role in bone development and bone fracture repair. Angiopoietin 1 (Ang1) is an endothelial growth factor essential for embryonic vascular development that generates a stable and functional vasculature via binding to the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and induces Tie2 phosphorylation. Recently, cartilage oligomeric matrix protein (COMP)-Ang1 was developed by replacing the N-terminal portion of Angiopeotin 1 with the short coiled-coil domain of cartilage oligomeric matrix protein, a chimeric protein of angiopoietin-1. COMP-Ang1 is known to have more soluble, stable and potent than did the native Ang1. The periodontal ligament cells (PDLCs) have different tendencies for osteogenesis, chondrogenesis, adipogenesis, or proliferation. The PDLCs have osteoblast-like properties, including the capacity to form mineralized nodules in vitro. A diversity of cellular characteristics can be controlled in part by the addition of cytokines, growth factors, or drugs. Therefore, understanding the exact roles of these factors and identifying the signal transduction pathways involved are to be the crucial events in controlling a balanced cellular differentiation. The main aims of this study were to evaluate the osteogenic capacity of COMP-Ang1 in bone tissue and to determine the osteogenic activity of COMP-Ang1 in vitro by estimating its effect on osteoblast differentiation using human PDLCs. In order to compare the phenotypes of wild type (WT) and COMP-Ang1 tissue-specific inducible (MT) mice in bones, this study used ovariectomy osteoporosis and calvarial bone defect models. The osteogenic capacity of COMP-Ang1 in bone tissue in vivo was also investigated using an 8 mm critical-sized calvarial defect model. Bone structure was evaluated using micro-computed tomography (CT) software, which calculates morphometirc parameters from a selected volume of interest (VOI). To confirm whether COMP-Ang1 regulates the expression of angiogenic and osteogenic genes, this study measured the mRNA expression levels in the scaffolds inserted in a rat calvarial defect model. In vitro differentiation potential of COMP-Ang1 recombinant protein was evaluated. In addition, this study evaluated the effect of COMP-Ang1 on migration using human PDLCs. As the results, MT mice did not show any increase in bone formation, compared to WT at a significant level. In contrast, the values of micro-CT revealed that MT group resulted in a significant increase in new bone formation, compared to control group in rats. Further, the expression levels of osteogenic genes, such as Runx2, Osx, and Bmp-2, and angiogenic genes, such as Pecam1 and Lyve1, were significantly up-regulated in the COMP–Ang1 group. Stimulating rat bone marrow derived cells (BMCs) with COMP-Ang1 up-regulated the expression of Runx2, Osx, and a stromal cell-derived factor (SDF-1) receptor, CXCR4 in a dose dependent manner. It was found that human PDLCs were migrated into COMP-Ang1-loaded scaffold and recruited through COMP-Ang1-mediated up-regulation of the SDF-1. Quantitative real-time RT–PCR revealed that the genes specific for c-Jun, FosB, and Fra1 were significantly induced by treatment with COMP-Ang1. These results suggest that COMP–Ang1 accelerates new bone formation through stimulation of osteogenesis and angiogenesis as well as the migration of progenitor cells. Collectively, these results demonstrate that COMP-Ang1 has a striking ability to stimulate bone formation, suggesting that COMP-Ang1 may be a useful as a therapeutic protein for bone repair.

COMP-Ang1의 허혈손상을 받은 다리에서 근육재생을 촉진하는 두 가지 기전에 관한 연구 : COMP-Ang1 accelerates regeneration of ischemia-damaged skeletal muscle through dual regulation : up-regulation of myogenic factor synthesis via N-cadherin signaling in muscle cells and

윤석원 서울대학교 대학원 2013 국내박사

Angiopoietin-1 (Ang1), one of the major angiogenic factors, is known to modulate vascular stability, endothelial cells differentiation and survival. However, the direct effect of Ang1 on myoblasts differentiation and the regulatory mechanism remain unclear. In this study, I analyzed the regulatory mechanism of COMP-Ang1 on myoblasts differentiation and found N-cadherin as its receptor required for skeletal muscle regeneration. Tie2 expressing macrophages (TEM), infiltrated by COMP-Ang1, were also found in ischemic muscle for myogenesis acceleration. The ischemic stress in hindlimb stimulated the deterioration of muscle quality and induced the infiltration of inflammatory cells. Interestingly, COMP-Ang1 contributed not only to increase of limb salvage but also significantly to generate regenerating muscle. COMP-Ang1 also increased myotube formation in vitro. Especially, COMP-Ang1 enhanced the expression of myogenin, which is one of important myogenic transcription factors. The mechanism of myogenin synthesis by COMP-Ang1 was regulated by p38MAPK and Ca2+ ion. Interestingly, COMP-Ang1 bound to myoblast surface through N-cadherin but not by M-cadherin and Integrin β 1. COMP-Ang1 increased the p38 MAPK activation through directly binding to N-cadherin and augmented the interaction between N-cadherin and p120-catenin. Moreover, myoblasts that had down-regulated N-cadherin expression by siRNA could not develop myotube despite of existence of COMP-Ang1 in vivo. On the other hand, COMP-Ang1 enhanced the infiltration of macrophages into ischemic muscle compared to control group. Especially, COMP-Ang1 increased the infiltration of TEM (F4/80+Tie2+CD31-) which expresses IGF1, a known myogenic factor, compared with inflammatory macrophage (F4/80+Tie2-CD31-, InfM). TEM isolated from ischemic muscle significantly enhanced the myogenesis of cocultured myoblasts more than both non-treated and InfM groups. Therefore, these results suggest that COMP-Ang1 is a myogenic factor, which acts directly through N-cadherin-p120-catenin-p38MAPK-myogenin axis in myoblasts, and indirectly stimulates TEM recruitment into ischemic muscle to augment acceleration of myogenesis process.

얕은아래쪽배벽동맥피판의 생존 향상을 위한 VEGF와 COMP-Ang1 유전자 치료

유은경 계명대학교 대학원 2006 국내석사

(Abstract) Partial necrosis of pedicle skin flaps remains a substantial problem in plastic and reconstructive surgery. Ischemia may jeopardize skin flap survival and result in flap necrosis. The primary causes of necrosis are inadequate arterial inflow, insufficient venous outflow, or both. Therefore, we investigated the potential of suing adenovirus vector encoding for adenovirus VEGF (AdVEGF), adenovirus COMP-Ang1 (AdCOMP-Ang1) gene in an attempt to promote the viability of the superficial inferior epigastric artery flap model in a rat model. The flap was pedicled solely on the right inferior epigastric vessels. The flap was designed so that only the medial branch of the epigastric artery supplied blood to the flap. In result, there was a significant increase in mean percentage of survival flap area by 62.7%, 79.1%, 69.7% in flaps transfected with adenovirus VEGF, COMP-Ang1, coadministraion of VEGF and COMP-Ang1 at 3 days. There was a significant increase in mean percentage of survival flap area by 89.8%, 91.1%, 94.8% at 7 days, 95.6%, 94.8%, 96.3% at 14 days. H&E staining analyses revealed that blood vessels were formed after AdVEGF, AdCOMP-Ang1 or AdVEGF plus AdCOMP-Ang1 than AdLac Z. The results of this study suggest the possibility of using adenovirus-mediated VEGF, COMP-Ang1 gene therapy to promote therapeutic angiogenesis in patients who undergo reconstructive procedures. (초 록) 피부피판의 생존을 높이기 위한 연구는 조직의 허혈을 개선하는데 역점을 두고 있다. 조직이 정상적인 기능을 하기 위해서는 혈관을 통한 산소와 영양분의 적당한 공급이 절대적으로 필요하기 때문이다. 조직이 저산소증에 처하였을 때 혈관신생을 촉진하는 내재적인 인자로 작용하는 것으로 vascular endothelial growth factor (VEGF), angiopoietin, transforming growth factor-beta 1 (TGF-β1), monocyte chemoattractant protein-1 (MCP-1)등이 알려져 있다. 이들 중 VEGF와 angiopoietin이 결합하여 작용을 나타내는 수용체가 혈관내피세포에만 선택적으로 존재하기 때문에 다른 촉진인자들에 비해 연구의 관심도가 크다. 본 연구의 목적은 adenovirus VEGF (AdVEGF)와 adenovirus COMP-angiopoietin1 (AdCOMP-Ang1)을 이용한 유전자치료가 얕은아래쪽배벽동맥피판의 생존을 향상시키는지를 알아보는 것이다. 백서의 하복부에서 일측의 SIEA에 의해서만 혈액을 공급 받는 피부피판을 3 × 6 cm 크기로 일으켜 혈액을 공급받지 못하는 쪽에 피판의 괴사를 유도하고, 괴사가 시작되는 부위의 피부피판에 AdVEGF와 AdCOMP-Ang1을 주사하여 이 유전자 치료가 피부피판의 생존율을 향상시키는지를 연구하였다. 대조군은 생리식염수를 같은 양으로 주사하였다. 피판의 생존을 3, 7, 14일에 육안적으로 관찰하고 Vistrak digitalⓇ을 이용하여 생존한 부위의 크기를 측정하였다. 조직을 생검하여 H&E로 염색하고 endothelial cell marker인 CD31 antibody를 이용한 면역조직화학염색법(immunohistochemistry; IHC)으로 혈관신생의 정도를 정량화하여 비교 분석하였다. 실험 결과 생존면적이 3일 째에 대조군에 비해 AdVEGF, AdCOMP-Ang1, AdVEGF와 AdCOMP-Ang1을 함께 투여한 그룹에서 각각 89.8%, 91.1%, 94.8%로 의미 있게 증가하였다. 7일 째는 각각 89.8%, 91.1%, 94.8%, 14일 째는 각각 95.6%, 94.8%, 96.3%로 생존면적이 증가한 것을 알 수 있었다. CD31을 이용한 IH에서 대조군에 비해 AdVEGF, AdCOMP-Ang1을 각각 투여한 그룹과 함께 투여한 그룹에서 CD31이 더 많이 발현하였다. 혈관의 수를 관찰한 결과 투여 후 3일에는 유의성이 없으나 7일과 14일에 있어서는 대조군에 비해 실험군에서 혈관의 수가 더 증가한 것을 알 수 있었다. 결론적으로 AdCOMP-Ang1과 AdVEGF가 혈관신생을 유도하여 피부피판 작성 초기인 7일째까지 피판의 생존율을 향상시키는 효과가 있었다.

Chlorhexidine 으로 유발된 Mouse의 복막경화증에서 angiopoietin-1 의 치료적 역할

이태환 전북대학교 대학원 2009 국내박사

복막경화증은 장기간 복막 투석 중 발생하는 복막 기능 저하의 중요한 병리 기전이다. 복막경화증은 복막의 혈관의 변화, 섬유화와 같은 복막의 구조적 변화와 관련되어 있다. 따라서 복막의 염증 반응을 조절할 수 있으면 복막경화증을 방지하는데 유익할 것이다. 혈관생성인자인 Angiopoietin (Ang)1은 혈관 내피세포에 대한 항염증작용과 항투과성작용을 가지고 있다. Ang1의 변형물질인 COMP-Ang1은 본래의 Ang1에 비해 일차 배양 혈관 내피세포에서 타이로신 키나아제 Tie2 수용체의 인산화 활성과 Akt를 통한 신호전달이 더 강력하다. 이 실험에서 COMP-Ang1이 chlorhexidine으로 유발된 복막경화 동물 모델에서 복막 의 섬유화를 감소시키는지에 대한 연구를 하였다. COMP-Ang1은 쥐에서 chlorhexidine에 의해 유발된 복막의 섬유화와 염증반응을 감소시키는 효과가 있었다. 또한 COMP-Ang1은 chlorhexidine으로 유발된 복막의 ICAM-1과 VCAM-1의 단백발현과 F4/80-양성 대식세포의 침윤을 완화시켰다. 결론적으로 COMP-Ang1이 chlorhexidine으로 유발되는 복막경화증을 보호하는 효과를 증명하였고, COPM-Ang1을 복막경화증의 치료에 있어서의 잠재성을 제시하였다. Sclerosing encapsulating peritonitis (SEP) has been recognized as a possible late complication of continuous ambulatory peritoneal dialysis (CAPD), may be a concern about the possibility of higher rates of morbidity and mortality. SEP is associated with obstructive symptoms peritoneal structure changes such as alteration of vasculature, inflammation and fibrosis. Thus, the regulation of peritoneal inflammatory reaction and preservation of vasculature may have a beneficial effect in preventing peritoneal sclerosis. Angiopoietin-1 (Ang1), an angiogenic factor, has been reported for anti-inflammatory and anti-permeability functions. Previous reports documented that COMP-Ang1, a variant of native Ang1, found to be more potent than native Ang1 in phosphorylating Tie2 and signalling via Akt in primary cultured endothelial cells. The present study investigated whether COMP-Ang1 affects the development of peritoneal fibrosis and inhibits inflammation in a chlorhexidine(CH)-induced sclerosing peritonitis mouse model. COMP-Ang1 significantly ameliorated the increased protein expression of intercellular adhesion molecule (ICAM)-1 in chlorhexidine-induced mice and also prevented the number of infiltrated F4/80-positive macrophages. Further it suppressed the chlorhexidine-induced cellular proliferation as measured by proliferating cell nuclear antigen (PCNA) expression in the peritoneum. These findings suggest that COMP-Ang1 having protective role against chlorhexidine-induced peritoneal sclerosis and may have a therapeutic value in the management of sclerosing encapsulating peritonitis by inhibiting inflammation.