Tenofovir Inhibits Wound Healing of Epithelial Cells and Fibroblasts from the Upper and Lower Human Female Reproductive Tract
| Autor: | Mickey V. Patel, Richard M. Rossoll, Marta Rodriguez-Garcia, Jack E. Bodwell, Charles R. Wira, Zheng Shen |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Anti-HIV Agents HIV Infections Cervix Uteri Endometrium Tenofovir alafenamide Article 03 medical and health sciences 0302 clinical medicine medicine Humans Secretion 030212 general & internal medicine Tenofovir Barrier function Cells Cultured Wound Healing Multidisciplinary Tight junction business.industry Epithelial Cells Genitalia Female Fibroblasts Epithelium 3. Good health 030104 developmental biology medicine.anatomical_structure Immunology Vagina Cancer research HIV-1 Female business Wound healing Elafin |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| Popis: | Disruption of the epithelium in the female reproductive tract (FRT) is hypothesized to increase HIV infection risk by interfering with barrier protection and facilitating HIV-target cell recruitment. Here we determined whether Tenofovir (TFV), used vaginally in HIV prevention trials, and Tenofovir alafenamide (TAF), an improved prodrug of TFV, interfere with wound healing in the human FRT. TFV treatment of primary epithelial cells and fibroblasts from the endometrium (EM), endocervix (CX) and ectocervix (ECX) significantly delayed wound closure. Reestablishment of tight junctions was compromised in EM and CX epithelial cells even after wound closure occurred. In contrast, TAF had no inhibitory effect on wound closure or tight junction formation following injury. TAF accumulated inside genital epithelial cells as TFV-DP, the active drug form. At elevated levels of TAF treatment to match TFV intracellular TFV-DP concentrations, both equally impaired barrier function, while wound closure was more sensitive to TFV. Furthermore, TFV but not TAF increased elafin and MIP3a secretion following injury, molecules known to be chemotactic for HIV-target cells. Our results highlight the need of evaluating antiretroviral effects on genital wound healing in future clinical trials. A possible link between delayed wound healing and increased risk of HIV acquisition deserves further investigation. |
| Databáze: | OpenAIRE |
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