Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)gove...Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)governs hair follicle development.FGF7 functions as a paracrine protein regulating epithelial proliferation,differentiation and migration.The single-cell transcriptome profling and immunofuorescence analysis demonstrated that FGF7 localizes at DPC,while FGF7 receptor(FGFR2)expresses in both DPC and HFSC.Through co-culture experiments of HFSC and DPC,the results indicated that FGF7 secreted from DPC promotes the proliferation of DPC and HFSC via Wnt signaling pathway and induces HFSC differentiation.Furthermore,CUT&Tag assay revealed genomic colocalization between FGF7 and pluripotency-related genes and GSK3β.Electrophoretic mobility shift assay(EMSA)demonstrated that FGF7 interacts with the promoter region of CISH and PRKX.This research provides valuable insights into the molecular mechanisms underlying the hair cycle.Understanding the interaction between HFSC and DPC,as well as the role of FGF7,may advance regenerative medicine and hair loss treatment.展开更多
Reactive astrocytes,which exhibit a correlation with the degeneration of dopaminergic neurons,are present in a considerable number during the progression of Parkinson’s disease(PD).However,the underlying factors shap...Reactive astrocytes,which exhibit a correlation with the degeneration of dopaminergic neurons,are present in a considerable number during the progression of Parkinson’s disease(PD).However,the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated.Here,we demonstrate that fibroblast growth factor 7(FGF7)/FGF receptor 2(FGFR2)autocrine signaling intensifies astrocyte reactivity and inflammation.Genetic deletion of Arrb2,ß-Arrestin2 encoding gene,led to escalated astrocyte reactivity in MPTP-treated mice,which was further substantiated in astrocyte-specific Arrb2 knockdown mice.RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity.Subsequently,conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes.Furthermore,deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice.Mechanistically,STAT1 was distinguished as the transcription factor suppressing Fgf7 expression,whileß-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220,an E3 ubiquitin ligase for STAT1.More importantly,selectively engaging dopamine D2 receptor(Drd2)/ß-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production,thereby restoring balance in astrocyte reactivity.Collectively,our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system,particularly within the context of PD.The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.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
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
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supported by the National Key Research And Development Program of China(2022YFD1300204)。
文摘Hair follicle stem cell(HFSC),capable of self-renewal and differentiation in hair follicle,represents an emerging stem cell model for regenerative medicine.The interaction between HFSC and dermal papilla cell(DPC)governs hair follicle development.FGF7 functions as a paracrine protein regulating epithelial proliferation,differentiation and migration.The single-cell transcriptome profling and immunofuorescence analysis demonstrated that FGF7 localizes at DPC,while FGF7 receptor(FGFR2)expresses in both DPC and HFSC.Through co-culture experiments of HFSC and DPC,the results indicated that FGF7 secreted from DPC promotes the proliferation of DPC and HFSC via Wnt signaling pathway and induces HFSC differentiation.Furthermore,CUT&Tag assay revealed genomic colocalization between FGF7 and pluripotency-related genes and GSK3β.Electrophoretic mobility shift assay(EMSA)demonstrated that FGF7 interacts with the promoter region of CISH and PRKX.This research provides valuable insights into the molecular mechanisms underlying the hair cycle.Understanding the interaction between HFSC and DPC,as well as the role of FGF7,may advance regenerative medicine and hair loss treatment.
基金supported by grants from the National Key R&D Program of China(No.2021ZD0202903)the National Natural Science Foundation of China(Nos.82373851,82173797,and 82204357)the Natural Science Foundation of Jiangsu Province(BK20231267,China).
文摘Reactive astrocytes,which exhibit a correlation with the degeneration of dopaminergic neurons,are present in a considerable number during the progression of Parkinson’s disease(PD).However,the underlying factors shaping astrocyte reactivity and neuroinflammation in PD remain inadequately elucidated.Here,we demonstrate that fibroblast growth factor 7(FGF7)/FGF receptor 2(FGFR2)autocrine signaling intensifies astrocyte reactivity and inflammation.Genetic deletion of Arrb2,ß-Arrestin2 encoding gene,led to escalated astrocyte reactivity in MPTP-treated mice,which was further substantiated in astrocyte-specific Arrb2 knockdown mice.RNA sequencing profiling of Arrb2 knockout astrocytes identified Fgf7 as a critical effector of astrocyte reactivity.Subsequently,conditional knockdown of Fgf7 and its receptor Fgfr2 in astrocytes elicited advantageous effects for MPTP-treated mice by restraining the inflammatory phenotypic transition of reactive astrocytes.Furthermore,deletion of astrocytic Fgf7 mitigated MPTP-induced pathology in Arrb2 knockout mice.Mechanistically,STAT1 was distinguished as the transcription factor suppressing Fgf7 expression,whileß-Arrestin2 counteracted the proteasomal degradation of STAT1 by binding to RNF220,an E3 ubiquitin ligase for STAT1.More importantly,selectively engaging dopamine D2 receptor(Drd2)/ß-Arrestin2-biased signaling using the agonist UNC9995 exhibited therapeutic potential in MPTP-treated mice via moderation of astrocytic FGF7 production,thereby restoring balance in astrocyte reactivity.Collectively,our study bridges a crucial knowledge gap by elucidating the novel functions of FGF family members within the central nervous system,particularly within the context of PD.The autocrine signaling of FGF7/FGFR2 represents a novel mechanism and a potential druggable target for modulating astrocyte-derived inflammation.
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.
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.
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。
