Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-β1-Induced Fibrosis in Keloids

Darmawan, Claudia C.; Montenegro, Sara E.; Jo, Gwanghyun; Kusumaningrum, Novi; Lee, Si Hyung; Chung, Jin Ho; Mun, Je‐Ho

doi:10.3390/ijms21082833

Cited by 15 publications

(11 citation statements)

References 28 publications

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“…Lesions were obtained for further analysis 7 days after the final treatment. Measurement of graft weight and western blot analysis of xenotransplant tissue was carried out according to a previously described protocol ( 14 ). The study was approved by the Institutional Care and Use Committee (IACUC) of Seoul National University, and the number of animals used was kept to a minimum to reduce suffering, according to the protocol.…”

Section: Methodsmentioning

confidence: 99%

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden

Darmawan¹,

Hur²,

Kusumaningrum³

et al. 2023

Acta Derm Venereol

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Keloids are skin tumours caused by aberrant growth of dermal fibroblasts. Cellular senescence contributes to aging and various pathological conditions, including cancer, atherosclerosis, and fibrotic diseases. However, the effects of cellular senescence and senolytic drugs on keloids remain largely unknown. This study investigated senescent fibroblasts in keloids and assessed the effects of dasatinib on these cells. Tissues acquired from keloid removal surgery were analysed for senescence-associated β-galactosidase-positive cells, p16 expression, and the effects of dasatinib treatment on keloids. Keloid tissue was xenotransplanted into mice, and the effect of intralesional dasatinib injection on keloid growth was observed. The results showed that the numbers of β-galactosidase-positive and p16-expressing cells were higher in the keloids compared with in the controls. Dasatinib induced selective clearance of senescent cells and decreased procollagen expression in cultured keloid fibroblasts. In this xenotransplant keloid mouse model, intralesional injection of dasatinib reduced gross keloid tissue weight and the expression of both procollagen and p16. In addition, dasatinib-treated keloid fibroblasts conditioned medium reduced procollagen and p16 expression in cultured keloid fibroblasts. In conclusion, these results suggest that an increased number of senescent fibroblasts may play an important role in the pathogenesis of keloids. Therefore, dasatinib could be an alternative treatment for patients with keloids.

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Section: Methodsmentioning

confidence: 99%

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden

Darmawan¹,

Hur²,

Kusumaningrum³

et al. 2023

Acta Derm Venereol

Self Cite

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“…The keloid xenograft mouse model was performed as previously described [20]. Briefly, the keloid tissues were cut into approximately 5 × 5 × 5 mm sections, and the weight was ranged from 0.08 to 0.1 g per tissue block.…”

Section: Keloid Xenograft Mouse Modelmentioning

confidence: 99%

Pinocembrin Ameliorates Skin Fibrosis via Inhibiting TGF-β1 Signaling Pathway

Zhai

et al. 2021

Biomolecules

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Skin fibrotic diseases, such as keloids, are mainly caused by pathologic scarring of wounds during healing and characterized by benign cutaneous overgrowths of dermal fibroblasts. Current surgical and therapeutic modalities of skin fibrosis are unsatisfactory. Pinocembrin, a natural flavonoid, has been shown to possess a vast range of pharmacological activities including antimicrobial, antioxidant, anti-inflammatory, and anti-tumor activities. In this study we explored the potential effect and mechanisms of pinocembrin on skin fibrosis in vitro and in vivo. In vitro studies indicated that pinocembrin dose-dependently suppressed proliferation, migration, and invasion of keloid fibroblasts and mouse primary dermal fibroblasts. The in vivo studies showed that pinocembrin could effectively alleviate bleomycin (BLM)-induced skin fibrosis and reduce the gross weight and fibrosis-related protein expression of keloid tissues in xenograft mice. Further mechanism studies indicated that pinocembrin could suppress TGF-β1/Smad signaling and attenuate TGF-β1-induced activation of skin fibroblasts. In conclusion, our results demonstrate the therapeutic potential of pinocembrin for skin fibrosis.

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“…The mechanism of fibrosis is similar for tissues and organs and consists of the following four sequential stages: (a) organ or tissue injury; (ii) inflammatory reactions of effector cells; (c) increased synthesis of extracellular matrix (ECM); and (d) tissue and organ structural remodelling disorders that ultimately lead to organ failure. APN and APN receptor agonists have strong anti‐fibrotic activity in the liver, lung, heart, skin and other organs and tissues 12‐16 . Recent studies found that APN also plays an important role in the process of renal fibrosis (Figure 1).…”

Section: Role Of Apn In Renal Fibrosismentioning

confidence: 99%

“…First, it promotes fatty acid oxidation and glucose metabolism and also regulates blood lipid metabo- lung, heart, skin and other organs and tissues. [12][13][14][15][16] Recent studies found that APN also plays an important role in the process of renal fibrosis (Figure 1). pathway has potential for the treatment of chronic renal fibrosis.…”

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confidence: 99%

Advances in understanding the role of adiponectin in renal fibrosis

et al. 2020

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Renal fibrosis is characterized by the proliferation of renal intrinsic cells, activation of renal interstitial fibroblasts and deposition of extracellular matrix (ECM), processes that lead to the progressive loss of renal function. Renal fibrosis is characterized by the proliferation of renal intrinsic cells, activation of renal interstitial fibroblasts, and septal fibrosis is recognized as a marker for the progression of chronic kidney disease, a condition that is associated with high morbidity and mortality and is a significant public health burden. Despite extensive studies, there are no effective treatments for renal fibrosis. Adiponectin (APN) is a protein mainly produced by adipocytes that has anti‐inflammatory and anti‐atherosclerotic effects, improves insulin resistance and provides other salutary effects. Recent studies found that APN can inhibit ECM deposition by inhibiting inflammation and oxidative stress, and by regulating the TGF‐β, AMPK, MCP‐1 and other signalling pathways. Many recent studies have examined the roles of these pathways in the pathogenesis of renal fibrosis. In this article, we review the pathogenic mechanism of APN in renal fibrosis and provide a theoretical basis for delaying and blocking renal fibrosis by alteration of APN activity.

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Adiponectin-Based Peptide (ADP355) Inhibits Transforming Growth Factor-β1-Induced Fibrosis in Keloids

Cited by 15 publications

References 28 publications

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden

Dasatinib Attenuates Fibrosis in Keloids by Decreasing Senescent Cell Burden

Pinocembrin Ameliorates Skin Fibrosis via Inhibiting TGF-β1 Signaling Pathway

Advances in understanding the role of adiponectin in renal fibrosis

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