Biochemical and Biophysical Research Communications
miR-145-5p attenuates hypertrophic scar via reducing Smad2/Smad3 expression
Introduction
Hypertrophic scar (HS), one of pathological scars, is the result of abnormal wound healing [1,2]. During the development of HS, abnormally enhanced activity and over-proliferation of many cells including fibroblasts are detected, leading to over-proliferation of dermal tissues and thus inducing HS [3,4]. Since the elasticity of scar tissues is reduced, the normal anatomical structure of skin tissues of the body surface is destroyed, which has bad effects on the good appearance and leads to different degrees of dysfunction of tissues and organs and even disability, thereby affecting the normal life and work of patients and damaging their physical and mental health status [5,6]. The etiology and molecular mechanisms leading to over-deposition of extracellular matrix (ECM) in HS remain unclear, which are great challenges for clinical treatment [[7], [8], [9]]. Currently, comprehensive treatments including surgery, silicone gel, drug therapy, laser therapy, radiotherapy, cryotherapy and compression therapy are adopted for the treatment of HS, but there is always no specific treatment [[10], [11], [12], [13], [14]]. Therefore, finding out specific treatments has been a major challenge in Department of Burns and Plastic Surgery. Recently, a lot of further studies on the genes and molecular mechanisms related to the pathogenesis of HS conducted by scholars have manifested that for the prevention and treatment of HS, the occurrence and development of abnormal scars should be avoided or reduced from the source, and finding out gene defects in HS and correcting from the genetic level are the premises of the breakthrough in the treatment of HS [[15], [16], [17], [18]].
Micro ribonucleic acids, a class of non-coding small-molecule RNAs with approximately 22 nucleotides in length, can identify and bind to related target genes in the form of complete or incomplete complementation [19], and adjust the expression quantities of genes and/or proteins at the post-transcriptional level via the cleavage or inhibition of the mRNA translation of target genes [[20], [21]]. Existing studies have demonstrated that miRNAs can modulate and control the occurrence of skin scars through various mechanisms [[22], [23], [24]]. MiR-145-5p functions an essential role in regulating the occurrence and development of various diseases [25,26], but its role in HS has not been studied.
The study aims to explore the function of miR-145-5p in HS. The results suggested that miR-145-5p directly targeted Smad2 and Smad3 and inhibited fibroblast activation and migration both in vivo and in vitro.
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Patients
In this study, 5 pairs of HS in the proliferative stage definitely diagnosed in clinic and normal skin tissue samples were collected from patients in the hospital from May 2018 to May 2019. Five subjects of either gender from the Department of Burns and Plastic Surgery signed the informed consent and aged 20–28 years old. Besides, the site of HS was limbs, chest and abdomen after burning and scalding. The course of disease was 3–8 months (Table 1). The scar tissues in the affected area met the
miR-145-5p arrested fibroblast proliferation and migration
To explore the role of miR-145-5p in fibrogenesis, RT-PCR was employed to measure the level of miR-145-5p in HS and normal skin of patients. HS showed less content of miR-145-5p than that of normal skin (Fig. 1A). Additionally, a significant lower expression of miR-145-5p of fibroblasts was found after cultured with transforming growth factor beta (TGF-β) for 1 day (Fig. 1B), which indicates that miR-145-5p participates in the development of scar formation. Fibroblasts were transfected with
Discussion
Skin scar refers to the phenomenon that the skin heals after burns but still has pathological features, of which the most common is HS based on reports [27,28]. In the past few decades, the advancement in the acute burn care has decreased the mortality rate of burns, but a wide range of scars is usually found on the skin surface of patients with large-area burns, causing pain and itching, and even affecting movement [29,30]. Scars lead to dramatically lower quality of life of many patients and
Declaration of competing interest
The authors declare that they have no conflict of interest.
Acknowledgments
None.
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