Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has...Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.展开更多
Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can ...Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu （ST 25） decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.展开更多
Suspended moxibustion can decrease the expression of prokineticin 1 and its receptor in colonic tissue from rats modeling chronic visceral hyperalgesia. This study aimed to verify if rat spinal cord prokineticin 1 and...Suspended moxibustion can decrease the expression of prokineticin 1 and its receptor in colonic tissue from rats modeling chronic visceral hyperalgesia. This study aimed to verify if rat spinal cord prokineticin 1 and its receptor contribute to the analgesic effect of suspended moxibustion in a rat model of irritable bowel syndrome where rats display chronic visceral hypersensitivity. Results showed that suspended moxibustion at Tianshu （ST25） point significantly decreased visceral sensitivity to colorectal distention in a chronic visceral hyperalgesia rat model; also protein and mRNA expression of prokineticin 1 and prokineticin receptor 1 in the spinal cord of rats was significantly decreased. Experimental findings indicate that prokineticin 1 and prokineticin receptor 1 are involved in the analgesia using suspended moxibustion in rats with chronic visceral展开更多
Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen ...Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.展开更多
文摘Objective: Prokineticin-1 (PROK1) is a recently described protein with a wide range of functions including tissue specific angiogenesis, modulation of inflammatory responses and regulation of haematopoiesis. PROK1 has been found in the steroidogenic organs like ovary, testis, adrenal and specially placenta and they have been found to have a role in development of the olfactory system and GnRH system. The aim was to update the role of PROK1 and PROK2 inhuman reproduction since the review was provided by Maldono-Perez (2007) on the potentials of prokineticins in reproduction. Design: A review of international scientific literature by a search of Pubmed and the authors files was done for citation of articles relevant to prokineticins in reproduction, be it its role in ovary, testis, uterus with special emphasis on implantation, normal pregnancy, in labour, pathophysiological states like tubal pregnancy, pcos, various genital tumours, and cases of isolated hypogonadotropic hypogonadism with mutations with PROK2/ PROKR2 and studies detailing functional mechanisms. Results: In the normal cycle, PROK1 has been found to have important roles in implantation, regulating several genes like COX-2, IL-8, IL-11, CTGF related to implantation. Initially murine studies revealed a critical role of PROK2 pathway on olfactory bulb morphogenesis and GnRH secretion which was accidentally discovered and since then several studies on mutations in PROK2/PROKR2 showed that they underlie some case of KS in humans. Although in mouse heterozygote state is not associated with clinical phenotype, most of human mutations are heterozygous. Conclusions: Role of PROK-1 in the process of implantation, with a deeper understanding of the process success rates in IVF and ART can be improved, besides understanding the pathophysiology of tubal pregnancy. Further presence in ovarian follicles of PROK1 can be used to plan a strategy for treating pcos. Development of antagonism of PROK’S may be a helpful strategy in treating preterm labour.
基金the National Basic Research Program of China (973 program), No.2009CB522900Shanghai Leading Academic Discipline Project, No. S30304+1 种基金 National Natural Science Foundation of China, No.81001549 Specialized Research Fund for the Doctoral Program of Higher Education, No.200802680001
文摘Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu （ST 25） decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.
基金supported by the National Basic Research Program of China (973 Program) (No. 2009CB522900)Nanjing University of Chinese Medicine, Key Laboratory of Acupuncture Combined with Medication (No. KJA200914)the National Natural Science Foundation of China (No. 30973783)
文摘Suspended moxibustion can decrease the expression of prokineticin 1 and its receptor in colonic tissue from rats modeling chronic visceral hyperalgesia. This study aimed to verify if rat spinal cord prokineticin 1 and its receptor contribute to the analgesic effect of suspended moxibustion in a rat model of irritable bowel syndrome where rats display chronic visceral hypersensitivity. Results showed that suspended moxibustion at Tianshu （ST25） point significantly decreased visceral sensitivity to colorectal distention in a chronic visceral hyperalgesia rat model; also protein and mRNA expression of prokineticin 1 and prokineticin receptor 1 in the spinal cord of rats was significantly decreased. Experimental findings indicate that prokineticin 1 and prokineticin receptor 1 are involved in the analgesia using suspended moxibustion in rats with chronic visceral
基金the National Natural Science Foundation of China(Grant No.81871148,No.81701539 and No.81571496).
文摘Varicocele is one of the most important causes of male infertility,as this condition leads to a decline in sperm quality.It is generally believed that the presence of varicocele induces an increase in reactive oxygen species levels,leading to oxidative stress and sperm apoptosis;however,the specific pathogenic mechanisms affecting spermatogenesis remain elusive.Prokineticin 2(PK2),a secretory protein,is associated with multiple biological processes,including cell migration,proliferation,and apoptosis.In the testis,PK2 is expressed in spermatocytes under normal physiological conditions.To investigate the role of PK2 in varicocele,a rat varicocele model was established to locate and quantify the expression of PK2 and its receptor,prokineticin receptor 1(PKR1),by immunohistochemistry and quantitative real-time PCR assays(qPCR).Moreover,H2O2 was applied to mimic the oxidative stress state of varicocele through coculturing with a spermatocyte-derived cell line(GC-2)in vitro,and the apoptosis rate was detected by flow cytometry.Here,we illustrated that the expression levels of PK2 and PKR1 were upregulated in the spermatocytes of the rat model.Administration of H202 stimulated the overexpression of PK2 in GC-2.Transfection of recombinant pCMV-HA-PK2 into GC-2 cells promoted apoptosis by upregulating cleaved-caspase-3,caspase-8,and B cell lymphoma 2-associated X;downregulating B cell lymphoma 2;and promoting the accumulation of intracellular calcium.Overall,we revealed that the varicocele-induced oxidative stress stimulated the overexpression of PK2,leading to apoptosis of spermatocytes.Our study provides new insight into the mechanisms underlying oxidative stress-associated male infertility and suggests a novel therapeutic target for male infertility.
