Induction of Apoptosis in Pterygium Cells by Antagonists of Growth Hormone–Releasing Hormone Receptors

Abstract

The aim of the study was to investigate the signaling of growth hormone-releasing hormone receptor (GHRH-R) in the pathogenesis of pterygium and determine the apoptotic effect of GHRH-R antagonist on pterygium epithelial cells (PECs). METHODS. Fourteen samples of primary pterygium of grade T3 with size of corneal invasion ‡ 4 mm were obtained for investigation by histology, immunofluorescence, electron microscopy, explant culture, and flow cytometry. RESULTS. We found that PECs were localized in the basal layer of the epithelium in advancing regions of the head of pterygium. These cells harbored clusters of rough endoplasmic reticulum, ribosomes, and mitochondria, which were consistent with their aggressive proliferation. Immunofluorescence studies and Western blots showed that GHRH-R and the downstream growth hormone receptor (GH-R) were intensively expressed in PECs. Their respective ligands, GHRH and GH, were also elevated in the pterygium tissues as compared to conjunctival cells. Explanted PECs were strongly immunoreactive to GHRH-R and exhibited differentiation and proliferation that led to lump formation. Treatment with GHRH-R antagonist MIA-602 induced apoptosis of PECs in a dose-dependent manner, which was accompanied by a downregulation of ERK1 and upregulation of Caspase 3 expression. CONCLUSIONS. Our results revealed that GHRH-R signaling is involved in survival and proliferation of PECs and suggest a potential therapeutic approach for GHRH-R antagonist in the treatment of pterygium.

Expression profiling suggests the involvement of hormone-related, metabolic, and Wnt signaling pathways in pterygium progression

“…Downregulated pathways also provide us with pieces of evidence of disease progression. Hormone-related pathways are significantly downregulated; some research reported that hormone-related growth factors and receptors are implicated in pterygium ( 45 , 46 ). Even though some hormones can affect corneal morphology, physiology, and metabolism, there is few of evidence indicating that hormones directly participate in the development of pterygium ( 47 , 48 ).…”

A novel role for Livin in the response to ultraviolet�B radiation and pterygium development

“…Pterygium is a fibrovascular neoformation composed of epithelium and highly vascular loose subepithelial connective tissue (20). Previous studies have demonstrated that apoptotic and oncogenic proteins, microsatellite instability, inflammatory mediators, extracellular matrix modulators, EMT and other factors are involved in the development of pterygium (4,(9)(10)(11)13). However, to the best of our knowledge, the precise molecular mechanisms of pterygium pathogenesis have not been resolved.…”

“…Pterygium exhibits tumor-like features, including propensity to invade normal tissue, recurrence after excision and coexistence with premalignant lesions (4,7,8). Previous studies have demonstrated that pterygium epithelial cells (PECs) are highly proliferative, have features of epithelial-mesenchymal transition (EMT) and overexpress anti-apoptotic proteins (9)(10)(11)(12)(13). Livin is a member of the inhibitors of apoptosis protein (IAP) family (14), which function in tumor initiation, progression and resistance to chemotherapy (15).…”

Uric acid–driven NLRP3 inflammasome activation triggers lens epithelial cell senescence and cataract formation

“…After organ culturing, selected lenses were sectioned for hematoxylin and eosin (H&E, C0105S, Beyotime) staining and urate deposition staining with Gomori methenamine silver (GMS, BB-44715, Bestbio, Shanghai, China), as we previously reported [ 11 , 46 ]. The lenses were fixed in 4% paraformaldehyde, dehydrated, embedded in paraffin, and sectioned coronally at 5 μm thickness.…”