Transforming growth factor-β (TGF-β) pathway presents dysregulation in pathological scarring and mediates hypertrophic scar (HS) formation.

A new study published in Advances in Clinical and Experimental Medicine analyzed the potential mechanism of long non-coding RNA NORAD (LncRNA NORAD) and microRNA (miR-26a) regulation of the TGF-β pathway in hypertrophic scar fibroblasts (HSFs).

In this experiment, hypertrophic scar tissues were collected and assayed for LncRNA NORAD, miR-26a, transforming growth factor β receptor I (TGF-βR1) and TGF-βR2, with enzyme-linked immunosorbent assay (ELISA) or qualitative polymerase chain reaction (qPCR). 

It was found that LncRNA NORAD is decreased, miR-26a is increased and TGF-β receptors show abnormal expression in scar tissue. While LncRNA NORAD knockdown inhibits proliferation of HSF cells induced by TGF-β1 treatment. Additionally, cell apoptotic levels are markedly increased and cell numbers in G0/G1 phase are higher. The TGF-β/Smad pathway is regulated by decreasing endogenous LncRNA NORAD levels, likely due to affecting the relative levels of TGF-βR1. Moreover, p21 is notably upregulated, while cyclin D1 and CDK4 are downregulated. Apoptosis-related proteins are significantly affected and RIP shows that miR-26a targets the 3UTRs of TGF-βR2 and UBE3A.

From the results, it was concluded that LncRNA NORAD regulates HSF proliferation via miR-26a mediating the regulation of TGF-βR2/R1. Therefore, LncRNA NORAD/miR-26a could be a potential target for treating HS.

Source: Advances in Clinical and Experimental Medicine. 2021 Apr;30(4):395-403. doi: 10.17219/acem/133482.