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Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing

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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.

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Acknowledgments

V.R.K. and M.M. are supported by senior research fellowships from the Council of Scientific and Industrial Research (CSIR), New Delhi, India. V.R.K. and P.S.K. thank Prof. A.B..Mandal, Director, CSIR–CLRI for his encouragement and support. The authors also thank Mr.C.Dilip Kumar, Biomaterials Department, CSIR–CLRI for his help in transportation of tissue samples.

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Authors and Affiliations

  1. Department of Biomaterials, CSIR - Central Leather Research Institute, Adyar, Chennai, 600020, Tamilnadu, India

    Venkat Raghavan Krishnaswamy & Purna Sai Korrapati

  2. Department of Genetics, Dr. ALM PG Institute of Basic Medical Sciences, University of Madras, Taramani Campus, Chennai, 600113, Tamilnadu, India

    Mayakannan Manikandan & Arasambattu Kannan Munirajan

  3. Department of General Surgery, St.Isabel Hospital, Chennai, 600004, Tamilnadu, India

    Doraiswamy Vijayaraghavan

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  1. Venkat Raghavan Krishnaswamy
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  2. Mayakannan Manikandan
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  3. Arasambattu Kannan Munirajan
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  4. Doraiswamy Vijayaraghavan
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  5. Purna Sai Korrapati
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Correspondence to Purna Sai Korrapati.

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Figure S1

Immunofluorescence studies on tissue sections showing diminished levels of DPT in (a) normal dermis, (b) CCW. The bright green fluorescence on the collagen fibers in the dermis are indicated by arrows. Scale bar 100 μm (JPEG 326 kb)

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Krishnaswamy, V.R., Manikandan, M., Munirajan, A.K. et al. Expression and integrity of dermatopontin in chronic cutaneous wounds: a crucial factor in impaired wound healing. Cell Tissue Res 358, 833–841 (2014). https://doi.org/10.1007/s00441-014-2000-z

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  • DOI: https://doi.org/10.1007/s00441-014-2000-z

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