Biological Characteristics And Related Molecular Mechanisms Of Pathologic Adipose Infiltration In Macrodactyly

Objective Macrodactyly is a rare congenital disease manifested as overgrowth of multiple tissues.The disease seriously affect the appearance and function,which is great challenge for plastic and hand surgeons.Due to the insufficiency investigation on molecular mechanism,cell biological and pathological features of adipose invasion,there is a great controversy about the surgical strategy and timing of debulking surgery.Thus,the gene expression profiles,cytological characteristics of Mac-ADSCs and fat infiltration of nerve tissue of the macrodactyly were investigated in the study.Methods Whole exon sequencing,sanger sequencing,c DNA microarray and other bioinformatics analysis were performed to identify mutations,gene expression and pathway connections in the pathological adipose tissues.The cell characteristics of the stem cells from the adipose tissue of the macrodactyly(Mac-ADSCs)was studied with normalabdominal subcutaneous adipose-derived stem cells(Sat-ADSCs)as control,including cell cycle,apoptosis and multiple differentiation induction.Electromyography(EMG)in patients with type 2 macrodactyly was examined.And the expression of neural proteins and ultrastructure changes were observed.Results The PIK3CA-C420 R and E81 K mutations were firstly found in macrodactyly patients.The expression of EGFL6,ANGPTL7,PTN,FGF1,SFRP4 and other genes were significantly up-regulated.MacADSCs showed an enhancement of proliferative activity as well as osteogenesis and cartilage differentiation potential,while the adipogenic differentiation potential was decreased.The myelin sheath injury,nerve regeneration and functional compensation was found co-existence in type2 macrodactyly patients.Conclusion PI3K-AKT pathway activated,cell secretion and ECM receptor interaction genes upregulated in macrodactyly adipose tissue,which could be the significant target for the medicinal development;The enhancement of osteogenesis,cartilage potential in Mac-ADSCs indicate that early defatting could effectively decrease progress of the disease;for type 2 macrodactyly patients,to preserve or resect the enlarged nerve should be determined according to the nerve injury and compensation situation.