Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

Shen, Chong; Jiang, Lifang; Shao, Huawei; You, Chuangang; Zhang, Guoliang; Ding, Shuting; Bian, Tingwei; Han, Chunmao

doi:10.1038/srep37553

Cited by 30 publications

(11 citation statements)

References 34 publications

(47 reference statements)

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“…Fibroblasts are the major effector cells in wound healing (21). In the process of hypertrophic scar formation, fibroblasts typically exhibit excessive proliferation, enhanced migration and inhibited apoptosis, and secrete abundant extracellular matrix (22,23). It was previously identified that miRNA molecules serve important roles in the biological functions of hypertrophic scar fibroblasts, but their mechanisms of action requires further elucidation (24).…”

Section: Discussionmentioning

confidence: 99%

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Wang

et al. 2019

Exp Ther Med

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The present study aimed to determine the expression of microRNA (miRNA or miR)-145 in hypertrophic scars at the tissue and cellular levels, and to investigate its biological functions and mechanism of action. A total of 36 patients who were diagnosed with hypertrophic scar were included in the present study. Reverse transcription-quantitative polymerase chain reaction was used to determine the expression of miR-145 in tissues and fibroblasts. Primary fibroblasts were transfected with negative control miRNA, miR-145 mimics or inhibitor. A Cell Counting Kit-8 assay was performed to determine the level of proliferation of fibroblasts. Flow cytometry was employed for cell cycles determination and apoptosis in fibroblasts. A Matrigel assay was used to evaluate the invasion ability of fibroblasts. Western blotting was used to determine the expression of the transcription factor SOX-9 (SOX-9) protein in fibroblasts. Rescue experiments were performed to examine the effect of SOX-9 on the regulation of fibroblasts by miR-145. The dual luciferase reporter assay was performed to identify the direct interaction between SOX-9 and miR-145. The expression of miR-145 was reduced in hypertrophic tissues and fibroblasts. Overexpression of miR-145 inhibited the proliferation, G1/S phase transition and invasion of fibroblasts, and promoted the apoptosis of fibroblasts. In addition, overexpression of miR-145 inhibited SOX-9 protein expression. By contrast, the expression of SOX-9 reversed the effects of miR-145 on the proliferation, cell cycle, apoptosis and invasion of fibroblasts. The miR-145 seed region was able to bind with the 3′-untranslated region of the SOX-9 mRNA to regulate its expression. The present study demonstrated that miR-145 expression is reduced in hypertrophic scar tissues and negatively associated with SOX-9 expression. In addition, miR-145 inhibits the proliferation, cell cycle and invasion, and promotes the apoptosis of fibroblasts by down-regulating the expression of SOX-9. The current study provides a potential target for the clinical diagnosis and treatment of hypertrophic scars.

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Section: Discussionmentioning

confidence: 99%

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Wang

et al. 2019

Exp Ther Med

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“…In contrast, RHA may provide a robust and effective treatment by directly targeting myofibroblasts with less toxicity to neighboring normal cells. Our recent finding that the RHA showed effective preventive function against the scar formation on rabbit ears could provide a support in verifying the specific function of RHA in potentially treating fibrotic organs.…”

Section: Resultsmentioning

confidence: 99%

Cells with Higher Cortical Membrane Tension Are More Sensitive to Lysis by Biosurfactant Di-rhamnolipids

Shen

Jiang

Long

et al. 2019

ACS Biomater. Sci. Eng.

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Tissue and cellular stiffening is associated with pathologies including fibrosis and cancer. Healthy cells also exhibit a wide range of membrane cortical tensions, which have been studied in the field of mechanobiology. Here, we quantify the mechanosensitivity of the lysis agent the di-rhamnolipid (RHA), which is a bacterially produced biosurfactant. RHA exhibited selective lysis correlated strongly with cortical membrane tension in osteoblasts, smooth muscle cells, fibroblasts, epithelial cells, and erythrocytes. Reducing cortical membrane tension by cytoskeleton inhibitors (cytochalasin D and nocodazole) or osmotic regulators (sucrose, polyethylene glycol, and nonionic surfactants) attenuated the RHA toxicity. The selective toxicity of RHA toward human chronic myeloid leukemia K562 cells over healthy blood cells suggests a potential therapy for blood cancer. Targeted killing of myofibroblasts transformed from either fibroblasts or epithelial cells indicates its antifibrotic effect. Combined, these studies showed the potential for specific targeting of cells with differential mechanical properties rather than chemical or biological pathways.

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“…43 After 72 h co-culture, the medium was discarded and the cells were incubated with calcein-AM/PI solution (3 μL AM and 3 μL PI in 3 mL PBS) for 20 min, and then washed three times in PBS before imaging under a fluorescence microscope (OLYMPUS I × 70). 44…”

Section: Methodsmentioning

confidence: 99%

Konjac glucomannan hydrogel dressing and its combination with Chinese medicine for the wound treatment

Zhao

Guo

et al. 2022

New J. Chem.

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Targeted killing of myofibroblasts by biosurfactant di-rhamnolipid suggests a therapy against scar formation

Cited by 30 publications

References 34 publications

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Decreased expression of microRNA‑145 promotes the biological functions of fibroblasts in hypertrophic scar tissues by upregulating the expression of transcription factor SOX‑9

Cells with Higher Cortical Membrane Tension Are More Sensitive to Lysis by Biosurfactant Di-rhamnolipids

Konjac glucomannan hydrogel dressing and its combination with Chinese medicine for the wound treatment

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