Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spe...Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.展开更多
研究丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)相关蛋白丝裂原活化蛋白激酶磷酸酶(mitogen activated protein kinase phosphatase-1,MKP-1)和磷酸化细胞外信号调节激酶(phosphorylation extracellular signal-regula...研究丝裂原活化蛋白激酶(mitogen activated protein kinase,MAPK)相关蛋白丝裂原活化蛋白激酶磷酸酶(mitogen activated protein kinase phosphatase-1,MKP-1)和磷酸化细胞外信号调节激酶(phosphorylation extracellular signal-regulated kinases,p-ERK1/2)在上皮性卵巢肿瘤组织及正常卵巢组织中的表达差异,并探讨其在卵巢癌发生、发展中的作用,为卵巢癌的治疗提供新的思路及实验依据。选取64例上皮性卵巢癌、35例卵巢上皮性交界瘤及32例卵巢上皮性良性肿瘤患者的组织,另选取26例正常卵巢组织作对照,进行MKP-1及p-ERK1/2的免疫组化分析,并同时对其中部分病例进行上述蛋白的western-blot研究。结果显示正常卵巢、良性肿瘤、交界瘤及卵巢癌组织MKP-1的表达依次递减,各组之间进行两两比较均有显著性差异(P<0.01),FIGOⅢ期与Ⅳ期卵巢癌组织MKP-1的表达显著低于Ⅰ期与Ⅱ期卵巢癌组织(P<0.01);而p-ERK1/2在正常卵巢、良性肿瘤、交界瘤及卵巢癌组织的表达依次递增,各组之间进行两两比较也均有显著性差异(P<0.01),FIGOⅢ期与Ⅳ期卵巢癌组织p-ERK1/2的表达显著高于Ⅰ期与Ⅱ期卵巢癌组织(P<0.01)。且免疫组化及western-blot均显示MKP-1与p-ERK1/2在卵巢癌组织中的表达存在显著的负相关性,(r=-0.90,P<0.01及r=-0.78,P<0.01)。本研究结果表明MKP-1与p-ERK1/2的异常表达可能跟上皮性卵巢肿瘤的发生、发展有关,它们之间的表达失衡可能是卵巢癌发生、发展的原因之一。展开更多
基金supported by the Research Foundation of Jilin Provincial Science&Technology Development(20210204164YY,YDZJ202201ZYTS524,20230204067YY,20230204069YY)Jilin Province Development and Reform Commission(2022C044-3)Fundamental Research Funds for the Central Universities(135131002)。
文摘Serine protease 50(PRSS50/TSP50)is highly expressed in spermatocytes.Our study investigated its role in testicular development and spermatogenesis.Initially,PRSS50 knockdown was observed to impair DNA synthesis in spermatocytes.To further explore this,we generated PRSS50 knockout(Prss50^(−/−))mice(Mus musculus),which exhibited abnormal spermatid nuclear compression and reduced male fertility.Furthermore,dysplastic seminiferous tubules and decreased sex hormones were observed in 4-week-old Prss50^(−/−)mice,accompanied by meiotic progression defects and increased apoptosis of spermatogenic cells.Mechanistic analysis indicated that PRSS50 deletion resulted in increased phosphorylation of extracellular signal-regulated protein kinases 1 and 2(ERK1/2)and elevated levels of MAP kinase phosphatase 3(MKP3),a specific ERK antagonist,potentially accounting for testicular dysplasia in adolescent Prss50−/−mice.Taken together,these findings suggest that PRSS50 plays an important role in testicular development and spermatogenesis,with the MKP3/ERK signaling pathway playing a significant role in this process.
