title: Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing.
abstract: Chronic cutaneous wound (CCW) is a major health care burden wherein the healing process is slow or rather static resulting in anatomical and functional restriction of the damaged tissue. Dysregulated expression and degradation of matrix proteins, growth factors and cytokines contribute to the disrupted and uncoordinated healing process of CCW. Therefore, therapeutic approaches for effective management of CCW should be focused towards identifying and manipulating the molecular defects, such as reduced bioavailability of the pro-healing molecules and elevated activity of proteases. This study essentially deals with assessing the expression and integrity of an extracellular matrix protein, Dermatopontin (DPT), in CCW using real-time quantitative reverse transcriptase PCR and immunological techniques. The results indicate that, despite DPT's high mRNA expression, the protein levels are markedly reduced in both CCW tissue and its exudate. To elucidate the cause for this contradiction in mRNA and protein levels, the stability of DPT is analyzed in the presence of wound exudates and various proteases that are naturally elevated in CCW. DPT was observed to be degraded at higher rates when incubated with certain recombinant proteases or chronic wound exudate. In conclusion, the susceptibility of DPT protein to specific proteases present at high levels in the wound milieu resulted in the degradation of DPT, thus leading to impaired healing response in CCW.
authors.affiliation: Department of Biomaterials, CSIR - Central Leather Research Institute, Adyar, Chennai, 600020, Tamilnadu, India.
authors.forename: Venkat Raghavan
authors.initials: VR
authors.lastname: Krishnaswamy
authors.forename: Mayakannan
authors.initials: M
authors.lastname: Manikandan
authors.forename: Arasambattu Kannan
authors.initials: AK
authors.lastname: Munirajan
authors.forename: Doraiswamy
authors.initials: D
authors.lastname: Vijayaraghavan
authors.forename: Purna Sai
authors.initials: PS
authors.lastname: Korrapati
mesh_terms: D000595:Amino Acid Sequence; D011508:Chondroitin Sulfate Proteoglycans / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004591:Electrophoresis, Polyacrylamide Gel; D016326:Extracellular Matrix Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D005780:Gelatin / Q000378:metabolism; D006801:Humans; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D059748:Proteolysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism* / Q000473:pathology*; D014357:Trypsin / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics; D014945:Wound Healing / Q000235:genetics; D014947:Wounds and Injuries / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; C082019:DPT protein, human; D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D005780:Gelatin; D014357:Trypsin; D020782:Matrix Metalloproteinases