The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19....The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.展开更多
To investigate the regulation of estrogen, progesterone and prolactin stimulating the development of mammary gland, the Kunming mice were used as experimental animals in this study.Through the ex-periment in vitro, th...To investigate the regulation of estrogen, progesterone and prolactin stimulating the development of mammary gland, the Kunming mice were used as experimental animals in this study.Through the ex-periment in vitro, the effect of mammogenic hormones were systematically investigated on expression of FGF7 and FGF10 and their receptor in different periods.The results are as follows:in mammary glands of mice, 17 beta-estradiol increased the expression of FGF7;progesterone did not affect the expression of FGF7;prolactin up-regulated the expression of FGF7 significantly in pregnancy and lac-tation.17 beta-estradiol increased the expression of FGF10;progesterone and prolactin reduced the expression of FGF10 significantly in virgin;prolactin significantly increased the expression of FGF10 in pregnancy.When 17 beta-estradiol in the body was in relatively high proportion, it would lower the ex-pression of KGFR;while 17 beta-estradiol in the body was in relatively low proportion, it would increase the expression of KGFR.Low concentration of progesterone increased the expression of KGFR and high progesterone did not affect the expression of KGFR.Prolactin increased the expression of KGFR significantly in pregnancy and lactation.展开更多
目的观察复方黄柏液对家兔皮肤破损创口愈合以及对肉芽组织中TGF-β1、VEGF、FGF-7表达的影响。方法 15只家兔随机分为5组,即对照组、京万红组、复方黄柏液0.3、0.2、0.1 m L组,用手术刀在每只家兔耳内侧做长方形切口复制皮肤切除性伤...目的观察复方黄柏液对家兔皮肤破损创口愈合以及对肉芽组织中TGF-β1、VEGF、FGF-7表达的影响。方法 15只家兔随机分为5组,即对照组、京万红组、复方黄柏液0.3、0.2、0.1 m L组,用手术刀在每只家兔耳内侧做长方形切口复制皮肤切除性伤口模型,分别使用复方黄柏液0.3、0.2、0.1 m L及京万红软膏外敷伤口,给药5 d,以肉芽组织覆盖率评价创面愈合情况,并通过免疫组化方法观察创口肉芽组织中TGF-β1、VEGF、FGF-7的表达。结果复方黄柏液可不同程度提高创口肉芽组织覆盖率,使创口肉芽组织中VEGF、FGF-7的表达增加,显著高于对照组(P<0.05,P<0.01)。结论复方黄柏液可明显促进肉芽组织增生,促进皮肤伤口的愈合。展开更多
基金This work was supported by grants from the National Key Research and Development Program of China(2020YFA0908200 and 2021YFA1101300)GuangDong Basic and Applied Basic Research Foundation(202201011198)+1 种基金Guangzhou Laboratory Key Research Foundation(TL22-21)R&D Program of Guangzhou National Laboratory(SRPG22-021).
文摘The angiotensin-converting enzyme 2(ACE2)is a primary cell surface viral binding receptor for SARS-CoV-2,so finding new regulatory molecules to modulate ACE2 expression levels is a promising strategy against COVID-19.In the current study,we utilized islet organoids derived from human embryonic stem cells(hESCs),animal models and COVID-19 patients to discover that fibroblast growth factor 7(FGF7)enhances ACE2 expression within the islets,facilitating SARS-CoV-2 infection and resulting in impaired insulin secretion.Using hESC-derived islet organoids,we demonstrated that FGF7 interacts with FGF receptor 2(FGFR2)and FGFR1 to upregulate ACE2 expression predominantly inβcells.This upregulation increases both insulin secretion and susceptibility ofβcells to SARS-CoV-2 infection.Inhibiting FGFR counteracts the FGF7-induced ACE2 upregulation,subsequently reducing viral infection and replication in the islets.Furthermore,retrospective clinical data revealed that diabetic patients with severe COVID-19 symptoms exhibited elevated serum FGF7 levels compared to those with mild symptoms.Finally,animal experiments indicated that SARS-CoV-2 infection increased pancreatic FGF7 levels,resulting in a reduction of insulin concentrations in situ.Taken together,our research offers a potential regulatory strategy for ACE2 by controlling FGF7,thereby protecting islets from SARS-CoV-2 infection and preventing the progression of diabetes in the context of COVID-19.
基金the National Natural Science Foundation of China (Grant No. 30671538)
文摘To investigate the regulation of estrogen, progesterone and prolactin stimulating the development of mammary gland, the Kunming mice were used as experimental animals in this study.Through the ex-periment in vitro, the effect of mammogenic hormones were systematically investigated on expression of FGF7 and FGF10 and their receptor in different periods.The results are as follows:in mammary glands of mice, 17 beta-estradiol increased the expression of FGF7;progesterone did not affect the expression of FGF7;prolactin up-regulated the expression of FGF7 significantly in pregnancy and lac-tation.17 beta-estradiol increased the expression of FGF10;progesterone and prolactin reduced the expression of FGF10 significantly in virgin;prolactin significantly increased the expression of FGF10 in pregnancy.When 17 beta-estradiol in the body was in relatively high proportion, it would lower the ex-pression of KGFR;while 17 beta-estradiol in the body was in relatively low proportion, it would increase the expression of KGFR.Low concentration of progesterone increased the expression of KGFR and high progesterone did not affect the expression of KGFR.Prolactin increased the expression of KGFR significantly in pregnancy and lactation.
文摘目的观察复方黄柏液对家兔皮肤破损创口愈合以及对肉芽组织中TGF-β1、VEGF、FGF-7表达的影响。方法 15只家兔随机分为5组,即对照组、京万红组、复方黄柏液0.3、0.2、0.1 m L组,用手术刀在每只家兔耳内侧做长方形切口复制皮肤切除性伤口模型,分别使用复方黄柏液0.3、0.2、0.1 m L及京万红软膏外敷伤口,给药5 d,以肉芽组织覆盖率评价创面愈合情况,并通过免疫组化方法观察创口肉芽组织中TGF-β1、VEGF、FGF-7的表达。结果复方黄柏液可不同程度提高创口肉芽组织覆盖率,使创口肉芽组织中VEGF、FGF-7的表达增加,显著高于对照组(P<0.05,P<0.01)。结论复方黄柏液可明显促进肉芽组织增生,促进皮肤伤口的愈合。
