ABSTRACT
This study investigated the potential role of MAPK signaling pathways in conjunctivochalasis (CCH). Twenty loose conjunctival biopsy samples from 20 CCH and 15 conjunctival biopsy samples from 15 normal controls (CON) were collected. The conjunctival fibroblasts were cultured in vitro. Immunofluorescence, ELISA, Western blot and reverse transcription-polymerase chain reaction (RT-PCR) were used. Our results showed that the expression of p-ERK, p-JNK, and p-p38 in CCH conjunctiva was significantly higher than that in CON group. The expression of p38 MAPK, JNK, and ERK proteins in CCH fibroblasts was significantly higher than that in CON group. The total expression of MAPK mRNA in CCH fibroblasts was significantly higher than that in CON group. The activated forms of p38 MAPK, JNK, and ERK proteins and mRNAs might up-regulate the expression of MMPs in CCH loose conjunctival tissue and fibroblasts, causing the degradation of collagen fibers and elastic fibers and promoting the occurrence of CCH. Our results deepen the understanding of CCH pathological mechanism.
ABSTRACT
AIM: To investigate the expression of matrix metalloproteinases 1 and 3 (MMP-1 and MMP-3) and their tissue inhibitors of metalloproteinases 1 and 3 (TIMP-1 and TIMP-3) in the conjunctiva of eyes with conjunctivochalasis (CCh). METHODS: The conjunctival tissue was obtained from the CCh patients and controls, the MMPs/TIMPs expression concentration was determined by enzyme-linked immuno-sorbent assay (ELISA) and immunofluorescence staining. The expression levels of MMPs/TIMPs in the CCh fibro-blasts were determined by analyzing its concentration in the cellular supernatant that was abstracted from the in vitro cultured CCh fibroblasts. RESULTS: MMP-1 and MMP-3 levels determined by ELISA were both significantly higher in the CCh group than that in the control group (P=0.042, 0.022, respectively), so was the levels of TIMP-1 (P=0.010). No significant difference in the expression of TIMP-3 in conjunctiva was found between the two groups (P=0.298). The expression of MMP-1 and MMP-3 were both up-regulated significantly in the CCh group (P=0.040, 0.001, respectively) on immuno-fluorescence staining. MMP-1 and MMP-3 expression in the fibroblasts were both significantly higher in the CCh group than that in the control group (P=0.027, 0.001, respectively), while neither the TIMP-1 nor TIMP-3 expression was significantly different between the two groups (P=0.421, 0.237, respectively). CONCLUSION: The overexpression of MMP-1 and MMP-3 in conjunctival tissue and fibroblasts may play an important role in the pathogenesis and development of CCh.