A Novel CD147 Inhibitor, SP-8356, Attenuates Pathological Fibrosis in Alkali-Burned Rat Cornea

International Journal of Molecular Sciences

Hwanse Bae¹  Chanmin Joung¹  Hyojin Noh¹  Kisoo Pahk¹  Won-Ki Kim¹  Jeein Jung¹  HwaYoung Song² 

[1] Institute for Inflammation Control, Korea University, Seoul 02841, Korea;Shinpoong Pharmaceutical Company, Ansan 15610, Korea;

关键词: corneal alkali burn;    corneal haze;    myofibroblast;    alpha-smooth muscle actin;    collagen type III;    matrix-metalloproteinase;   

DOI  :  10.3390/ijms21082990

来源: DOAJ

【 摘 要 】

The corneal fibrotic responses to corneal damage often lead to severe corneal opacification thereby resulting in severe visual impairment or even blindness. The persistence of corneal opacity depends heavily on the activity of corneal myofibroblast. Myofibroblasts are opaque and synthesize a disorganized extracellular matrix (ECM) and thus promoting opacification. Cluster of differentiation 147 (CD147), a member of the immunoglobulin superfamily, is known to play important roles in the differentiation process from fibroblast to myofibroblast in damaged cornea and may therefore be an effective target for treatment of corneal opacity. Here, we examined the therapeutic efficacy of novel CD147 inhibiting verbenone derivative SP-8356 ((1S,5R)-4-(3,4-dihydroxy-5-methoxystyryl)-6,6-dimethylbicyclo[3.1.1]hept-3-en-2-one) on corneal fibrosis. Topical SP-8356 significantly reduced corneal haze and fibrosis in the alkali-burned cornea. In detail, SP-8356 inhibited both alpha-smooth muscle actin (α-SMA) expressing myofibroblast and its ECM-related products, such as matrix-metalloproteinase-9 and collagen type III and IV. Similar to SP-8356, topical corticosteroid (prednisolone acetate, PA) also reduced the ECM-related products and opacification. However, prednisolone acetate failed to decrease the population of α-SMA-positive corneal myofibroblast. In conclusion, SP-8356 is capable enough to prevent corneal haze by preventing pathological fibrosis after severe corneal damage. Therefore, SP-8356 could be a potentially promising therapeutic drug for corneal fibrosis.

【 授权许可】

Unknown