Hydroxycamptothecin Prevents Fibrotic Pathways in Fibroblasts In Vitro

Abstract

Peritendinous fibrosis, which leads to impaired tendon function, is a clinical problem worldwide, and it is urgent to explore potential ways to reduce the formation of peritendinous adhesion. Several studies have demonstrated the biological roles of hydroxycamptothecin (HCPT) in inhibiting fibrosis in different tissues. In this study, we investigated whether HCPT could inhibit tendon fibrosis in vitro. Our results revealed that HCPT inhibited transforming growth factor (TGF)‐β1‐induced cell viability of human fibroblasts, decreased excessive cell hyperproliferation and promoted fibroblasts apoptosis. In addition, HCPT treatment also inhibited expression of fibrosis genes COL3A1 and α‐smooth muscle actin (α‐SMA). In terms of mechanism, we pretreated fibroblasts with the endoplasmic reticulum stress (ER) inhibitor salubrinal and RNA‐dependent protein kinase‐like ER kinase (PERK) short hairpin RNA, these treatments abolished the inhibitory effects of HCPT on fibrosis, thereby suggesting that HCPT's inhibition of TGF‐β1‐induced tendon fibrosis might be mediated by the PERK signaling pathway in vitro. In conclusion, our results suggested that HCPT had protective effects on peritendinous tissue fibrosis and might be promising in future clinical applications. © 2019 IUBMB Life, 71(5):653–662, 2019

Hydroxycamptothecin Inhibits Peritendinous Adhesion via the Endoplasmic Reticulum Stress-Dependent Apoptosis

“…These data indicates that the ATF-6 partial pathway is activated and involved in the inhibition of fibrosis by HCPT. Based on our previous research (Yao et al, 2019) and the above findings, the potential pathway by which HCPT inhibits tendon fibrosis is presented in Figure 7 .…”

“…Our previous studies demonstrated that HCPT regulates proliferation and apoptosis in fibroblast and thus has the potential to prevent tendon adhesion (Yao et al, 2019). In this study, using a rat tendon injury model, we observed that 0.1 mg/ml HCPT significantly inhibited peritendinous adhesion 3 weeks after injury.…”

“…Similarly, it has also been reported to prevent postoperative glaucoma scar adhesion by inducing apoptosis of human tendon capsule fibroblasts (Yin et al, 2013). Our previous study showed that HCPT may have beneficial effects on tendon adhesion by inducing apoptosis in human fibroblasts (Yao et al, 2019), however, the mechanism may require further investigation.…”

“…Recent work has confirmed that ATF-6 and IRE1 and their downstream molecules play important roles in ER-induced apoptosis (Senkal et al, 2011; Zhang et al, 2018; Chern et al, 2019; Zhang et al, 2019). In addition, HCPT was reported to induce fibroblast apoptosis through the PERK pathway in vitro (Yao et al, 2019). However, the entire mechanism remains to be further investigated.…”

A phlorotannins‐loaded homogeneous acellular matrix film modulates post‐implantation inflammatory responses

“…This phenomenon is a normal part of the wound healing process after tissue injury or surgical repair (Chen et al., 2019; Hsu et al., 2018). Although adhesion is an essential step during surgical wound healing, excessive progression can cause severe postoperative adhesion at the operated site, which is accompanied by several complications such as a limited range of motion, pain, loss of function, and the need for additional surgery (e.g., tenolysis and scar release) (Chou et al., 2017; Yao, Zheng, Zhang, et al., 2019). Particularly, postoperative peritendinous adhesion (PPA) is often caused by physical trauma involving the flexor digitorum profundus or flexor digitorum superficialis tendons (Chen et al., 2014; MengQing et al., 2020).…”