CAJ | 학술논문

目的探讨胶质细胞源性神经营养因子(glial cell line-derived neurotrophic factor,GDNF)及其受体alpha 1(glial cell line-derived neurotrophic factor family receptor alpha 1,GFRα1)和受体酪氨酸激酶(receptor tyrosine kinase,RET)在小鼠肾发育过程中的表达和作用.方法应用免疫组织化学和蛋白印迹技术对胚龄(embryonic days,E)12 d、14 d、16 d、18 d胎鼠和生后(neonatal days,N)1 d、7 d、14 d、21 d、40 d仔鼠肾组织中GDNF、GFRα1和RET的表达进行定位观察和定量检测.结果免疫组化结果:在肾早期发生过程中,GDNF、GFRα1和RET均有表达.输尿管芽可见GDNF、GFRα1和RET的微弱表达;生后肾组织可见GDNF和GFRα1的微弱表达.肾小体发育过程中,在小泡体、逗号小体和S小体阶段可见GDNF和GFRα1的表达明显增强;在毛细血管袢期肾小体和未成熟期肾小体可见GDNF和GFRα1的表达减弱;肾小体发育成熟后,可见GDNF和GFRα1的表达消失.肾泌尿小管发育过程中,在肾小管(近端小管和远端小管)可见GDNF和GFRα1的表达;在集合管可见GDNF、GFRα1和RET的表达.在成熟肾中,GDNF和GFRα1定位表达于肾小管和集合管;RET定位表达于集合管.蛋白印迹结果:随着肾逐渐发育成熟,GDNF、GFRα1和RET在肾中表达量先递增, GDNF在E 18 d时表达量最高,GFRα1和RET在N 1 d时表达量最高;随后,GDNF、GFRα1和RET在肾中表达量逐渐减少.结论 GDNF/GFRα1/RET信号通路对肾发育各阶段及成熟肾功能的维持起重要作用.
목적 탐토효질세포원성신경영양인자(glial cell line-derived neurotrophic factor,GDNF)급기수체alpha 1(glial cell line-derived neurotrophic factor family receptor alpha 1,GFRα1)화수체락안산격매(receptor tyrosine kinase,RET)재소서신발육과정중적표체화작용.방법 응용면역조직화학화단백인적기술대배령(embryonic days,E)12 d、14 d、16 d、18 d태서화생후(neonatal days,N)1 d、7 d、14 d、21 d、40 d자서신조직중GDNF、GFRα1화RET적표체진행정위관찰화정량검측.결과 면역조화결과:재신조기발생과정중,GDNF、GFRα1화RET균유표체.수뇨관아가견GDNF、GFRα1화RET적미약표체;생후신조직가견GDNF화GFRα1적미약표체.신소체발육과정중,재소포체、두호소체화S소체계단가견GDNF화GFRα1적표체명현증강;재모세혈관번기신소체화미성숙기신소체가견GDNF화GFRα1적표체감약;신소체발육성숙후,가견GDNF화GFRα1적표체소실.신비뇨소관발육과정중,재신소관(근단소관화원단소관)가견GDNF화GFRα1적표체;재집합관가견GDNF、GFRα1화RET적표체.재성숙신중,GDNF화GFRα1정위표체우신소관화집합관;RET정위표체우집합관.단백인적결과:수착신축점발육성숙,GDNF、GFRα1화RET재신중표체량선체증, GDNF재E 18 d시표체량최고,GFRα1화RET재N 1 d시표체량최고;수후,GDNF、GFRα1화RET재신중표체량축점감소.결론 GDNF/GFRα1/RET신호통로대신발육각계단급성숙신공능적유지기중요작용.
Objective To investigate expressionsand role of glial cell line-derived neurotrophic factor (GDNF),GDNF family receptor alpha l (GFRα1) and RET in the development of mice kidney.Methods Immunohistochemistry and Western blot were used to detect the expressions of GDNF, GFRα1 and RET in E 12 d, E 14 d, E 16 d, E 18 d, N 1 d, N 7 d, N 14 d, N 21 d and N 40 d mice kidneys.Results The results showed that GDNF, GFRα1and RET were expressed in the early stage of renal development. The weak expressions of GDNF, GFRα1and RET were detected in the ureter bud, and the weak expressions of GDNF and GFRα1 were detected in metanephrogenic tissue. During the development process of renal corpuscles, GDNF and GFRα1 were expressed obviously in vesicle bodies, comma-shaped bodies and S-shaped bodies, while they were expressed weakly in capillary loop stage and immature renal corpuscles. With the mature of renal corpuscles, expressions of GDNF and GFRα1 disappeared. During the development process of uriniferous tubule, GDNF and GFRα1 were expressed in renal tubules (proximal tubule and distal tubule); GDNF, GFRα1 and RET were expressed in collecting ducts. In mature kidney, GDNF and GFRα1 were expressed in renal tubules and collecting ducts, RET was expressed in collecting ducts. Western blot results showed that, with the development of kidney, the expressions of GDNF, GFRα1 and RET increased atfirst, and reached to the peak at E 18 d (GDNF) and N 1 d (GFRα1 and RET). Then, expressions of GDNF, GFRα1 and RET in kidney decreased along with neonatal age.Conclusion GDNF/GFRα1/RET signaling pathway plays an important role in different development stages of kidney and in maintaining the function of mature kidney.