机构：[1]Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China.[2]Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.[3]The fourth affiliated hospital of Hebei Medical University, Shijiazhuang, China.河北医科大学第四医院
Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGF beta 1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome.
基金：
NIAMS from the NIDCR [R01DE019108, R01 AR060055]; NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASESUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) [R01AR060055, R01AR060055, R01AR060055, R01AR060055, R01AR060055] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE019108, R01DE019108, R01DE019108, R01DE019108, R01DE019108, R01DE019108, R01DE019108, R01DE019108] Funding Source: NIH RePORTER; NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Institute of Dental & Craniofacial Research (NIDCR) [R01DE019108, R01DE019108, R01DE019108] Funding Source: NIH RePORTER
第一作者机构：[1]Department of Preventive Dentistry, Peking University School and Hospital of Stomatology, National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing, China.[2]Department of Periodontics, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
