http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Jun Koo Yi,Zae Young Ryoo 한국동물생명공학회(구 한국동물번식학회) 2011 발생공학 국제심포지엄 및 학술대회 Vol.2011 No.1
alcineurin (CN) is a calcium and calmodulin-depedent serine/threonine phosphatase. CN plays an important role in various biological processes including cell proliferation, cardiovascular, skeletal muscle development and apoptosis. In rheumatoid arthritis (RA), CN plays a role synoviocyte activation and arthritis progression. The selective inhibition of CN by the over-expression of CN-binding protein 1 (Cabin1). In the present study, joint restricted transgenic mice expressing the human Cabin1(hCabin1) were generated, driven by type II collagen promoter and efficiency of these mice was investigated by experimental arthritis. These transgenic mice successfully expressed hCabin1 in joint tissue as well as other organs like the liver, the heart, and the brain. The joint specific over-expression of hCabin1 reduced the disease severity during collagen-induced arthritis. In fibroblast-like synoviocytes (FLSs) from hCabin1 transgenic mice, the productions of these cytokines including, TNF-α, IL-1β and IL-6 were decreased and MMPs was also depressed in transgenic mice FLS. In addition, the expression of proapoptotic p53, p21, caspase-3, caspase-9 and Bax increased in transgenic mice, indicating that hCabin1 may induce FLS death by regulating the expression of Bcl-2, p53, p21, caspase-3, casepase-9 and Bax. It is expected that these findings will provide a more knowledge about the pathogenic mechanisms of rheumatoid arthritis and a potential animal model of the choronic inflammatory conditions, including atherosclerosis and transplantation.
Cabin1 Regulates FLS Apoptosis and Inflammation in Mice with Collagen Induced Arthritis
Jun Koo Yi,Zae Young Ryoo 한국동물번식학회 2012 Reproductive & Developmental Biology(Supplement) Vol.36 No.2s
Calcineurin-binding protein 1 (Cabin1) regulates calcineurin phosphatase activity as well as the activation, apoptosis, and inflammatory responses of fibroblast-like synoviocytes (FLSs), which actively participate in the chronic inflammatory responses in rheumatoid arthritis (RA). However, the mechanism of action of Cabin1 in FLS apoptosis is not clear. The aim of this study was to define the regulatory role of Cabin1 in FLSs of mice with collagen-induced arthritis (CIA). Transgenic mice overexpressing human Cabin1 in joint tissues, under the control of a type II collagen promoter, were generated. hCabin1 expression in joints and FLSs was determined by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analysis. The expression of cytokines, matrix metalloproteinases (MMPs), and apoptosis-related genes in FLSs was determined by enzyme- linked immunosorbent assay, gelatin zymography, and RT-PCR, respectively. Joints were histologically examined after H&E and TRAP staining. hCabin1-transgenic CIA mice had less severe arthritis than wild-type CIA mice, based on hind paw thickness and histology. This was accompanied by significantly enhanced apoptosis in transgenic mice, evidenced by significantly more TUNEL-positive cells in synovial tissues. The expression of inflammatory cytokines and MMPs was reduced, and the transgenic CIA mice exhibited decreased Akt activation and increased expression of p53, caspase-3, caspase-9, and Bax. hCabin1 plays a critical role in promoting apoptosis of FLSs and in attenuating inflammation and the destruction of cartilage and bone in RA. These findings help elucidate the pathogenic mechanisms of RA and suggest that Cabin1 is a potential target for RA treatment.
Yi, Jun‐,Koo,Kim, Hei‐,Jung,Yu, Dong‐,Hoon,Park, Seo‐,Jin,Shin, Mi‐,Jung,Yuh, Hyung‐,Soo,Bae, Ki‐,Beom,Ji, Young‐,Rae,Kim, Na‐,Ri,Park, Si‐ Wiley Subscription Services, Inc., A Wiley Company 2012 Vol.64 No.7
<P><B>Abstract</B></P><P><B>Objective</B></P><P>Calcineurin‐binding protein 1 (CABIN‐1) regulates calcineurin phosphatase activity as well as the activation, apoptosis, and inflammatory responses of fibroblast‐like synoviocytes (FLS), which actively participate in the chronic inflammatory responses in rheumatoid arthritis (RA). However, the mechanism of action of CABIN‐1 in FLS apoptosis is not clear. This study was undertaken to define the regulatory role of CABIN‐1 in FLS from mice with collagen‐induced arthritis (CIA).</P><P><B>Methods</B></P><P>Transgenic mice overexpressing human CABIN‐1 in joint tissue under the control of a type II collagen promoter were generated. Expression of human CABIN‐1 (hCABIN‐1) in joints and FLS was determined by reverse transcription–polymerase chain reaction (RT‐PCR) and Western blot analysis. The expression of cytokines, matrix metalloproteinases (MMPs), and apoptosis‐related genes in FLS was determined by enzyme‐linked immunosorbent assay, gelatin zymography, and RT‐PCR, respectively. Joints were stained with hematoxylin and eosin and with tartrate‐resistant acid phosphatase for histologic analysis.</P><P><B>Results</B></P><P>Human CABIN‐1–transgenic mice with CIA had less severe arthritis than wild‐type mice with CIA, as assessed according to hind paw thickness and histologic features. The milder arthritis was accompanied by significantly enhanced apoptosis in transgenic mice, evidenced by a significantly greater number of TUNEL‐positive cells in synovial tissue. Expression of inflammatory cytokines and MMPs in the transgenic mice with CIA was reduced, and they exhibited decreased Akt activation and increased expression of p53, caspase 3, caspase 9, and Bax.</P><P><B>Conclusion</B></P><P>Our findings demonstrate that hCABIN‐1 plays a critical role in promoting apoptosis of FLS and in attenuating inflammation and cartilage and bone destruction in RA. These results help elucidate the pathogenic mechanisms of RA and suggest that CABIN‐1 is a potential target for treatment of this disease.</P>