Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal＇s lifetime, Adult Drosophila Malpighian tubu...Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal＇s lifetime, Adult Drosophila Malpighian tubules （MTs or fly kidney） are maintained by renal and nephric stem cells （RNSCs） via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inacti- vation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts （RBs）, the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.展开更多
目的探讨通心络胶囊对大鼠肾缺血再灌注损伤(R IR I)的保护作用及其可能的作用机制。方法将30只雄性W istar大鼠随机分为假手术组、缺血再灌注组和缺血再灌注+通心络预处理组,各10只。缺血再灌注组和缺血再灌注+通心络预处理组采用无损...目的探讨通心络胶囊对大鼠肾缺血再灌注损伤(R IR I)的保护作用及其可能的作用机制。方法将30只雄性W istar大鼠随机分为假手术组、缺血再灌注组和缺血再灌注+通心络预处理组,各10只。缺血再灌注组和缺血再灌注+通心络预处理组采用无损伤动脉夹夹闭大鼠双侧肾蒂45 m in,再灌注24 h的方法制成急性肾缺血再灌注损伤(AR IR I)模型,其中缺血再灌注+通心络预处理组术前喂通心络7 d。假手术组仅游离双侧肾蒂,暴露60 m in后再关闭切口。光镜下观察细胞结构改变;测定血肌酐(Cr);苏木精-伊红(HE)染色观察肾小管损伤程度;免疫组化图像分析光镜下Bc l-2阳性表达;一步法TUNEL细胞凋亡检测(TUNEL法)肾小管上皮细胞中凋亡阳性细胞;激光共聚焦显示肾小管上皮细胞凋亡情况。结果缺血再灌注组和缺血再灌注+通心络预处理组Cr及肾小管损伤评分较假手术组高(P<0.05);缺血再灌注+通心络预处理组Cr及肾小管损伤评分较缺血再灌注组低(P<0.01)。假手术组肾小管上皮细胞Bc l-2有少量表达;缺血再灌注组Bc l-2在肾小管上皮细胞的表达较假手术组增加(P<0.05);缺血再灌注+通心络预处理组Bc l-2在肾小管上皮细胞的表达较缺血再灌注组增加(P<0.01)。缺血再灌注组凋亡阳性细胞数明显多于假手术组(P<0.05),多见于肾小管,尤其是远端小管细胞,少数见于近端小管,而肾间质、肾小球极少见;缺血再灌注+通心络预处理组阳性细胞数明显少于缺血再灌注组(P<0.01)。结论通心络胶囊对大鼠AR IR I具有保护作用,其作用机制可能是通过上调Bc l-2在肾小管上皮细胞的表达,抑制肾小管上皮细胞凋亡而实现的。展开更多
基金supported by grants from the National Natural Science Foundation of China(No.31271582)Temasek Life Sciences Laboratory and Singapore Millennium FoundationBeijing Municipal Commission of Education(No.010135336400)
文摘Tissue homeostasis, accomplished through the self-renewai and differentiation of resident stem cells, is critical for the maintenance of adult tissues throughout an animal＇s lifetime, Adult Drosophila Malpighian tubules （MTs or fly kidney） are maintained by renal and nephric stem cells （RNSCs） via self-renewing divisions, however, it is unclear how RNSC proliferation and differentiation are regulated. Here we show that EGFR/MAPK signaling is dispensable for RNSC maintenance, but required for RNSC proliferation in vivo. Inacti- vation of the EGFR/MAPK pathway blocks or greatly retards RNSC cell cycle progression; conversely, over-activation of EGFR/MAPK signaling results in RNSC over-proliferation and disrupts the normal differentiation of renablasts （RBs）, the immediate daughters of RNSC divisions. Our data further suggest that EGFR/MAPK signaling functions independently of JAK/STAT signaling and that dMyc and CycE partially mediate EGFR/MAPK signaling in MTs. Together, our data suggest a principal role of EGFR/MAPK signaling in regulating RNSC proliferation, which may provide important clues for understanding mammalian kidney repair and regeneration following injury.
文摘目的探讨通心络胶囊对大鼠肾缺血再灌注损伤(R IR I)的保护作用及其可能的作用机制。方法将30只雄性W istar大鼠随机分为假手术组、缺血再灌注组和缺血再灌注+通心络预处理组,各10只。缺血再灌注组和缺血再灌注+通心络预处理组采用无损伤动脉夹夹闭大鼠双侧肾蒂45 m in,再灌注24 h的方法制成急性肾缺血再灌注损伤(AR IR I)模型,其中缺血再灌注+通心络预处理组术前喂通心络7 d。假手术组仅游离双侧肾蒂,暴露60 m in后再关闭切口。光镜下观察细胞结构改变;测定血肌酐(Cr);苏木精-伊红(HE)染色观察肾小管损伤程度;免疫组化图像分析光镜下Bc l-2阳性表达;一步法TUNEL细胞凋亡检测(TUNEL法)肾小管上皮细胞中凋亡阳性细胞;激光共聚焦显示肾小管上皮细胞凋亡情况。结果缺血再灌注组和缺血再灌注+通心络预处理组Cr及肾小管损伤评分较假手术组高(P<0.05);缺血再灌注+通心络预处理组Cr及肾小管损伤评分较缺血再灌注组低(P<0.01)。假手术组肾小管上皮细胞Bc l-2有少量表达;缺血再灌注组Bc l-2在肾小管上皮细胞的表达较假手术组增加(P<0.05);缺血再灌注+通心络预处理组Bc l-2在肾小管上皮细胞的表达较缺血再灌注组增加(P<0.01)。缺血再灌注组凋亡阳性细胞数明显多于假手术组(P<0.05),多见于肾小管,尤其是远端小管细胞,少数见于近端小管,而肾间质、肾小球极少见;缺血再灌注+通心络预处理组阳性细胞数明显少于缺血再灌注组(P<0.01)。结论通心络胶囊对大鼠AR IR I具有保护作用,其作用机制可能是通过上调Bc l-2在肾小管上皮细胞的表达,抑制肾小管上皮细胞凋亡而实现的。
