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Effects Of Cardiotonic Steroids On Dermal Collagen Synthesis And Wound Healing, Nasser El-Okdi, Sleiman Smaili, Vanamala Raju, Amjad Shidyak, Shalini Gupta, Larisa Fedorova, Jihad Elkareh, Sankaridrug Periyasamy, Anna Shapiro, M. Kahaleh, Deepak Malhotra, Jingwei Xie, Khew Chin, Joseph Shapiro

Jingwei Xie

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. …