Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic ski...Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.展开更多
The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote stru...The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.展开更多
基金supported by the Key Program of Yunnan Applied Basic Research Project(202301AS070036)Outstanding Youth Program of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202301AY070001-301)+2 种基金First-Class Discipline Team of Skin&Mucosal Regenerative Medicine of Kunming Medical University(2024XKTDTS10)National Natural Science Foundation of China(32360138,32301054,32060212,82371567)Program of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation(202301AY070001-012,202101AY070001-006,202301AY070001-198,202101AY070001-035,202101AY070001-036,202401AY070001-028,202401AY070001-068)。
文摘Individuals with diabetes frequently face serious challenges,including delayed wound healing and increased risk of infection.Notably,the regeneration of hair follicles plays a crucial role in accelerating diabetic skin damage repair,reducing the risk of infection,and enhancing overall skin health.Research has predominantly emphasized the re-epithelialization of diabetic wounds,with a paucity of in-depth studies on hair follicle regeneration.In the current study,we explored the effects of a bioactive amphibian-derived peptide,Cy_(RL-QN15),on promoting hair regeneration in a diabetic skin model.In vivo experiments demonstrated that local treatment with Cy_(RL-QN15)not only accelerated wound healing of scalded skin on the backs of diabetic Kunming(KM)mice but also improved growth of damaged hair follicles.Additionally,back-shaved diabetic C57BL/6 mice showed a significant increase in the growth of newly formed hair after 28 days of continuous Cy_(RL-QN15)treatment.Further analysis indicated that the hairregenerating effects of Cy_(RL-QN15)were closely associated with the proliferation and migration of hair follicle stem cells(HFSCs).Cy_(RL-QN15)enhanced intracellularβ-catenin expression by binding to the Frizzled-7 receptor on the surface of HFSCs.The up-regulation inβ-catenin modulated the levels of downstream proteins,such as cMYC,Cyclin D1,and Lef1,ultimately inducing hair regeneration.This study not only reveals the robust effects of the bioactive peptide Cy_(RL-QN15)in hair follicle regeneration but also provides novel avenues for the development of more targeted and effective therapeutics for diabetic wound healing in the future.
基金supported by the National Natural Science Foundation of China,Nos.32060212(to YW),81760648(to XWY),81560118(to BYZ)Project of Yunnan Applied Basic Research Project-Kunming Medical University Union Foundation,Nos.202101AY070001-006(to XWY)and 2018FE001(-161)(to JS)+2 种基金Yunnan Applied Basic Research Project Foundation,No.2019FB128(to YW)Project of Yunnan Province Clinical Research Centerfor Chronic Kidney Disease,No.202102AA10060(to BYZ)a grant from Scientific Research Foundation of Department of Education of Yunnan Province,No.2021J0205(to SSL)。
文摘The regenerative capacity of the central nervous system is very limited and few effective treatments are currently available for spinal cord injury.It is therefore a priority to develop new drugs that can promote structural and functional recovery after spinal cord injury.Previous studies have shown that peptides can promote substantial repair and regeneration of injured tissue.While amphibians have a pronounced ability to regenerate the spinal cord,few studies have investigated the effect of amphibian spinal cord-derived peptides on spinal cord injury.Here we report for the first time the successful identification and isolation of a new polypeptide,VD11(amino acid sequence:VDELWPPWLPC),from the spinal cord of an endemic Chinese amphibian(Odorrana schmackeri).In vitro experiments showed that VD11 promoted the secretion of nerve growth factor and brain-derived neurotrophic factor in BV2 cells stimulated with lipopolysaccharide,as well as the proliferation and synaptic elongation of PC12 cells subjected to hypoxia.In vivo experiments showed that intravertebral injection of VD11 markedly promoted recovery of motor function in rats with spinal cord injury,alleviated pathological damage,and promoted axonal regeneration.Furthermore,RNA sequencing and western blotting showed that VD11 may affect spinal cord injury through activation of the AMPK and AKT signaling pathways.In summary,we discovered a novel amphibian-derived peptide that promotes structural and functional recovery after spinal cord injury.