MiR-133a-3p inhibits scar formation in scalded mice and suppresses the proliferation and migration of scar derived-fibroblasts by targeting connective tissue growth factor

Abstract

Excessive scar formation post burn injury can cause great pain to the patients.MiR-133a-3p has been demonstrated to be anti-fibrotic in some fibrosis-related diseases. However, its possible role in scar formation has not been elucidated yet. In present study, the effect of miR-133a-3p on scar formation was investigated in a scalded model of mice. Moreover, the function of miR-133a-3p on proliferation and migration of scar-derived fibroblasts (SFs) was studied in vitro. It was found that miR-133a-3p was dramatically downregulated in scar tissue of scalded mice.Upregulation of miR-133a-3p by miR-133a-3p agomir obviously inhibited the scar formation in scalded mice. Histological staining showed that upregulation of miR-133a-3p attenuated the excessive deposition of collagen in scar tissue of scalded mice. In vitro study showed that upregulation of miR-133a-3p effectively suppressed the proliferation and migration of SFs. Besides, upregulation of miR-133a-3p attenuated the protein levels of α-smooth muscle actin (α-SMA) and collagen I, indicating that miR-133a-3p could suppress the activation of SFs. The expression of connective tissue growth factor (CTGF), a critical mediator in cell proliferation, migration and extracellular matrix (ECM) synthesis, was also downregulated by the upregulation of miR-133a-3p. Luciferase reporter assay validated that CTGF was directly targeted by miR-133a-3p. In addition, overexpression of CTGF abolished the effect of miR-133a-3p on inhibiting the proliferation, migration and activation of SFs, indicating that miR-133a-3p functioned by targeting CTGF. Therefore, miR-133a-3p might be a promising target for treating pathological scars.

Nanosized Shikonin-Fe(III) Coordination Material for Synergistic Wound Treatment: An Initial Explorative Study

“…Scald or fire burn is a common thermal injury in daily life, which may cause acute inflammatory pain, severe infection, and even death of burnt patients. 36 Since good antibacterial and anti-inflammation properties and low cytotoxicity of Shik-Fe were demonstrated above, the in vivo feasibility of Shik-Fe dressings for the treatment of scald wound was evaluated here. A round scald wound with a diameter of about 14 mm was formed on the back of Balb/c mice, and the mice were divided into four groups: untreated (control), GelMa (blank), Shik (Shik ointment, Beijing Tongrentang), and Shik-Fe to verify the efficacy of these treatments.…”

“…Scald or fire burn is a common thermal injury in daily life, which may cause acute inflammatory pain, severe infection, and even death of burnt patients . Since good antibacterial and anti-inflammation properties and low cytotoxicity of Shik-Fe were demonstrated above, the in vivo feasibility of Shik-Fe dressings for the treatment of scald wound was evaluated here.…”

α2-Antiplasmin as a Potential Therapeutic Target for Systemic Sclerosis

“…MiR-30c also prevents pro-fibrotic changes such as myofibroblast differentiation, ECM overproduction, and vascular dysfunction, and exerts anti-fibrotic and anti-angiopathic effects in SSc model mice [ 151 ]. Furthermore, miR-133a-3p, miR-26a, and miR-30a attenuate fibrosis progression by inhibiting CTGF [ 152 , 153 , 154 ]. CTGF has been reported to induce α2AP expression [ 11 ].…”