Brain research bulletin · 2026
HSP47 inhibitor Col003 inhibits glial scar formation and improves neurological function in ischemic stroke in rats.
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Zhou Kejian, Xie Yuliang, Xie Xiaoyun, Li Haoying, Liang Tingting, Li Jinpin, Liu Jingli
Аннотация
BACKGROUND: Glial scarring is a major obstacle for axonal regeneration and neural repair in the late stage of ischemic stroke. Reactive astrocytes are the main component of the glial scar. Heat shock protein 47 (HSP47) is significantly expressed in reactive astrocytes and remains present in the glial scar. However, the role of HSP47 in glial scar formation in ischemic stroke remains unclear.
METHODS: HSP47 was identified in the peri-infarct region of rats at 1, 7, and 14 days post middle cerebral artery occlusion (MCAO). The rats received daily tail vein injections of the HSP47 inhibitor Col003 from days 1-14 following MCAO. Glial scar, brain atrophy volume, neurological score was detected after ischemia.
RESULTS: HSP47 levels were increased in the peri-infarct area at 1, 7, and 14 days post-MCAO, as did those in astrocytes subjected to oxygenglucose deprivation/reoxygenation (OGD/R). The HSP47 inhibitor Col003 enhanced neurological functional recovery and minimized glial scar formation. Col003 inhibited the proliferation and migration of OGD/R-induced astrocytes and reduced the expression of glial fibrillary acidic protein, neurocan, and phosphacan. RNA-seq analysis revealed that differentially expressed genes in the Col003 treatment group were enriched in the JAK2/STAT3 pathway, which is associated with astrogliosis and glial scar formation.
CONCLUSION: Our findings demonstrated that Col003 inhibited JAK2/STAT3 phosphorylation in OGD/R-induced astrocytes. The HSP47 inhibitor Col003 might suppress astrocyte proliferation, migration, and glial scar formation through the JAK2/STAT3 pathway following ischemic stroke, which suggests a novel therapeutic strategy for the chronic phase of ischemic stroke.
METHODS: HSP47 was identified in the peri-infarct region of rats at 1, 7, and 14 days post middle cerebral artery occlusion (MCAO). The rats received daily tail vein injections of the HSP47 inhibitor Col003 from days 1-14 following MCAO. Glial scar, brain atrophy volume, neurological score was detected after ischemia.
RESULTS: HSP47 levels were increased in the peri-infarct area at 1, 7, and 14 days post-MCAO, as did those in astrocytes subjected to oxygenglucose deprivation/reoxygenation (OGD/R). The HSP47 inhibitor Col003 enhanced neurological functional recovery and minimized glial scar formation. Col003 inhibited the proliferation and migration of OGD/R-induced astrocytes and reduced the expression of glial fibrillary acidic protein, neurocan, and phosphacan. RNA-seq analysis revealed that differentially expressed genes in the Col003 treatment group were enriched in the JAK2/STAT3 pathway, which is associated with astrogliosis and glial scar formation.
CONCLUSION: Our findings demonstrated that Col003 inhibited JAK2/STAT3 phosphorylation in OGD/R-induced astrocytes. The HSP47 inhibitor Col003 might suppress astrocyte proliferation, migration, and glial scar formation through the JAK2/STAT3 pathway following ischemic stroke, which suggests a novel therapeutic strategy for the chronic phase of ischemic stroke.