Jagged 1 And Epidermal Growth Factor Promote Hair Growth In Mice

Hair follicles are mammalian skin accessory organs and the important part of maintaining skin homeostasis.For animals,the derivative of the hair follicle is clothing hair,which plays an important role in protecting against cold,defense,protection,and transmission,and is also one of the important animal products.For human beings,hair is an important part of appearance beauty,which affects the physical and mental health,and has important social significance.In recent years,the population of hair loss in the world has increased,and the population of hair loss in our country has increased year by year and tends to be younger.Therefore,the research on the treatment of hair loss has attracted the attention of researchers at home and abroad.Hair is the product of hair follicle growth and development.The normal development and cycle of hair follicle morphology involves many signal pathways and growth factors.Epidermal growth factor(EGF)is an important growth factor.The presence of a large number of EGF and EGF receptors on the outer root sheath of mature hair follicles indicates that EGF participates in the growth and development of hair follicles.Jagged 1 is one of the major ligands of the Notch receptor.It is widely expressed in a variety of tissues and participates in the development and growth of various tissues.It plays an important role in blood vessels,muscles,nerves and hematopoietic processes.Studies have shown that regulatory T cells(T-regs)play an important role in the growth and development of hair follicles.In addition,it has been found that T-reg cells can be regulated by ligands(Jagged 1)that highly express the Notch pathway.The growth of hair follicles suggests that Jagged 1 may stimulate the proliferation and differentiation of Hair follicle stem cells(HFSC),thereby promoting hair follicle regeneration.In order to investigate the therapeutic effects of Jagged 1and EGF on alopecia model mice and the effect on the hair follicle hair shaft growth in vitro,the following studies were performed in this experiment:(1)Jagged 1 and EGF promote androgen-inhibited hair follicle hair shaft growth in vitro8-week-old male C57 BL / 6 mice were used in the experiment.Intact hair follicles were isolated from the mouse tentacle pads and cultured.To explore the effective inhibitory concentration of testosterone(Testo)on the growth and development of hair follicles in vitro,whether Jagged 1 and EGF can promote the development of hair follicles inhibited by Testo.The results showed that when the concentration of Testo was above 20 ?g / m L,Testo significantly inhibited the growth of hair follicle hair shafts in vitro(P<0.05);after the addition of 40 ?g / m L Jagged1 or / and 1 ng / m L EGF,the hair follicle hair shaft grew faster and the hair shaft growth length was significantly higher Testo group(P<0.05).The results suggest that Jagged 1 and EGF may act as a growth factor to promote hair follicle growth in vitro.(2)Effect of Jagged 1 and EGF on hair growth in androgenetic alopecia miceIn the experiment,fifty 8-week-old male C57 BL / 6 mice were used as animal models.2cm × 2cm area hair was removed from the back of the mice and divided into control group,Testo group,Testo + Jagged 1 group,Testo + EGF group and Testo + Jagged 1 + EGF group,except for the control group,the other groups were first coated with 100 ?L 0.5% Testo in the hair removal area to inhibit the growth of follicles.After 1 hour,the three treatment groups were coated with 100 ?L of 1 mg /m L Jagged 1,30?g / m L EGF and 1mg / m L Jagged 1 + 30?g / m L EGF,once a day,apply continuously for 14 days and observe,and take photos of the mice on the 0,7,14 days of treatment.On the 7th and 14 th days of treatment,the skin tissues of mice in each group were collected,and the tissues were embedded in paraffin sections,HE staining,immunohistochemistry,and TUNEL analysis;The relative expression of Notch1,Notch2,Fibroblast growth factor 7(FGF 7),Sonic hedgehog(Shh),Vascular endothelial growth factor(VEGF),?-catenin,Tumor necrosis factor-?(TNF-?)and Induced synergistic stimulating molecule(Icos)was measured.The results show that Jagged 1 or / and EGF can promote hair growth in the back of mice with Testo-inhibited hair follicles,and the treatment in the Jagged 1+ EGF group is the best.The number of hair follicles in the group was significantly more than that in the Testo group(P<0.05).The thickness of the subcutaneous tissue in the Jagged 1+ EGF group was significantly higher than that in the Testo group(P<0.05).The expression of Ki67 was significantly higher than that in the Testo group(P<0.05);on the 14 th day of treatment,the apoptosis of hair follicle cells in the three treatment groups showed a downward trend but no significance compared with the Testo group(P>0.05).The results of RT-q PCR showed that the expression of Icos gene in the Jagged1 group was significantly increased(P <0.05),and the expressions of VEGF and TNF-? in the Jagged 1 + EGF group were significantly increased(P <0.05).There was no significant change in the expressions of Shh,FGF 7 and ?-catenin between the groups.On the 14 th day of treatment,Testo promoted the expression of Notch 1and Notch 2,Shh,FGF 7,TNF-? and Icos(P <0.05).These results suggest that Jagged 1 and EGF can promote hair growth in the back of mice,which may be achieved by stimulating cell proliferation and regulating the genes which involved in hair follicle growth and differentiation.This study demonstrates the effects of growth factors Jagged 1 and / or EGF on hair growth,providing an experimental basis for studying hair growth in animals,and providing new options for the development of new drugs for the treatment of androgenetic alopecia.