Effects of cardiotonic steroids on dermal collagen synthesis and wound healing
| Autor: | Shalini Gupta, Amjad Shidyak, Deepak Malhotra, Sankaridrug M. Periyasamy, M. Bashar Kahaleh, Larisa Fedorova, Zijian Xie, Sleiman Smaili, Khew Voon Chin, Vanamala Raju, Anna P. Shapiro, Nasser El-Okdi, Jihad Elkareh, Joseph I. Shapiro |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Digoxin medicine.medical_specialty Cardiotonic Agents Proline Physiology medicine.medical_treatment Bufanolides Gene Expression Ouabain Steroid Cardiac Glycosides Rats Sprague-Dawley Fibrosis Physiology (medical) Internal medicine Image Processing Computer-Assisted medicine Animals Humans Oligonucleotide Array Sequence Analysis Skin Wound Healing Cardiotonic steroids Dose-Response Relationship Drug integumentary system Chemistry Articles Fibroblasts medicine.disease Rats src-Family Kinases Endocrinology Collagen Signal transduction Wound healing medicine.drug |
| Zdroj: | Journal of Applied Physiology. 105:30-36 |
| ISSN: | 1522-1601 8750-7587 |
| DOI: | 10.1152/japplphysiol.00119.2008 |
| Popis: | We previously reported that cardiotonic steroids stimulate collagen synthesis by cardiac fibroblasts in a process that involves signaling through the Na-K-ATPase pathway (Elkareh et al. Hypertension 49: 215–224, 2007). In this study, we examined the effect of cardiotonic steroids on dermal fibroblasts collagen synthesis and on wound healing. Increased collagen expression by human dermal fibroblasts was noted in response to the cardiotonic steroid marinobufagenin in a dose- and time-dependent fashion. An eightfold increase in collagen synthesis was noted when cells were exposed to 10 nM marinobufagenin for 24 h ( P < 0.01). Similar increases in proline incorporation were seen following treatment with digoxin, ouabain, and marinobufagenin (10 nM × 24 h, all results P < 0.01 vs. control). The coadministration of the Src inhibitor PP2 or N-acetylcysteine completely prevented collagen stimulation by marinobufagenin. Next, we examined the effect of digoxin, ouabain, and marinobufagenin on the rate of wound closure in an in vitro model where human dermal fibroblasts cultures were wounded with a pipette tip and monitored by digital microscopy. Finally, we administered digoxin in an in vivo wound healing model. Olive oil was chosen as the digoxin carrier because of a favorable partition coefficient observed for labeled digoxin with saline. This application significantly accelerated in vivo wound healing in rats wounded with an 8-mm biopsy cut. Increased collagen accumulation was noted 9 days after wounding (both P < 0.01). The data suggest that cardiotonic steroids induce increases in collagen synthesis by dermal fibroblasts, as could potentially be exploited to accelerate wound healing. |
| Databáze: | OpenAIRE |
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