Platelet-rich plasma and platelet-derived lipid factors induce different and similar gene expression responses for selected genes related to wound healing in rat dermal wound environment
MOLECULAR BIOLOGY RESEARCH COMMUNICATIONS
Authors: Akbas, Fahri; Ozdemir, Busra; Bahtiyar, Nurten; Arkan, Hulya; Onaran, Ilhan
Abstract
Although platelet-rich plasma (PRP) is the plasma fraction that contains higher levels of platelet-sequestered proteins such as growth factors and chemokines, it is also abundant in bioactive lipids whose role in wound healing has not been well characterized. This study provides a preliminary evaluation for the effect of the lipid component of PRP on selected genes related to wound healing. Sprague-Dawley rats were classified into four groups after induction of full thickness excisional wounds: the lipid fraction (LF) (lipid extract from PRP) group, PRP group, dimethyl sulfoxide group, and sham group. Subsequently, relevant groups were topically treated with test preparations. Healing wounds were collected on 3rd, 7th and 14th days, and expression levels of 12 genes were determined using qPCR. LF treatment-induced gene expression signature distinct from that induced by PRP treatment, although there are some overlaps in LF- and PRP-responsive genes. Differentially expressed all eight genes (Cxcl5, Cxc11, Egfr, Tgfb1, IL10, Tgfa, Mmp1, and Mmp7) to LF response were significantly down-regulated at either 3rd, 7th, or 14th days. Also, the comparison between LF- and PRP-treatment groups showed that the LF significantly decreased expression of Cxcl11, Mmp7, and Tgfa mRNA on day 7 of healing. This study revealed that PRP and its LF induced different and similar gene expression responses of the skin during the repair of full thickness excisional wounds. Identifying mRNA response to LF treatment at whole transcriptome level can be beneficial for comprehensive understanding of the role of platelet-derived lipid factors in wound healing processes.
The level of synovial AXL expression determines the outcome of inflammatory arthritis, possibly depending on the upstream role of TGF-beta 1
RHEUMATOLOGY
Authors: Waterborg, Claire E. J.; Broeren, Mathijs G. A.; Davidson, Esmeralda N. Blaney; Koenders, Marije I.; van Lent, Peter L. E. M.; van den Berg, Wim B.; van der Kraan, Peter M.; van de Loo, Fons A. J.
Abstract
Objective. To investigate the role of AXL, a member of the anti-inflammatory TYRO3, AXL MER (TAM) receptor family, in arthritis. Methods. KRN serum transfer arthritis was induced in Axl(-/-) and wild-type mice. Knee and ankle joints were scored macro- and microscopically. Synovial gene and protein expression of Axl was determined in naive and TGF-beta 1-overexpressing joints. AXL expression was determined in Ml-like or M2-like macrophages and RA synovium. Human macrophages, fibroblasts and synovial micromasses were stimulated with TGF-beta 1 or the AXL inhibitor R428. Results. Ankle joints of Axl(-/-) mice showed exacerbated arthritis pathology, whereas no effect of Axl gene deletion was observed on gonarthritis pathology. To explain this spatial difference, we examined the synovium of naive mice. In contrast to the knee, the ankle synovial cells prominently expressed AXL. Moreover, the M2-like macrophage phenotype was the dominant cell type in the naive ankle joint. Human M2-like macrophages expressed higher levels of AXL and blocking AXL increased their inflammatory response. In the murine ankle synovium, gene expression of Tgfb1 was increased and Tgbl correlated with Axl. Moreover, TGFB1 and AXL expression also correlated in human RA synovium. In human macrophages and synovial micromasses, TGF-beta 1 enhanced AXL expression. Moreover, TGF-beta 1 overexpression in naive murine knee joints induced synovial AXL expression Conclusion. Differences in synovial AXL expression are in accordance with the observation that AXL dampens arthritis in ankle, but not in knee joints. We provide evidence that the local differences in AXL expression could be due to TGF-beta 1, and suggest similar pathways operate in RA synovium.