Poly‐L‐Lactic acid increases collagen gene expression and synthesis in cultured dermal fibroblast (Hs68) through the TGF‐β/Smad pathway

• DOI: 10.1111/jocd.15571
• Publication Date: 2022-12-28T07:36:45Z
• Authors: Wenqing Zhu; Chengzhi Dong
• Keywords: 0301 basic medicine; Tissue Inhibitor of Metalloproteinase-2; Tissue Inhibitor of Metalloproteinase-1; Polyesters; Gene Expression; Smad Proteins; Fibroblasts; Collagen Type I; Elastin; 03 medical and health sciences; Transforming Growth Factor beta; Humans; Collagen; RNA, Messenger; Matrix Metalloproteinase 1; Cells, Cultured; Procollagen

AbstractObjectivePoly‐L‐Lactic Acid (PLLA) is a synthetic polymer which possesses biocompatible and biodegradable properties, and is widely used in the clinical filler material. This study focuses on the potential role of PLLA on the collagen production of dermal fibroblasts and its mechanism.MethodsThe dermal fibroblast Hs60 was treated with different concentration of PLLA. RT‐qPCR was conducted for the determination of mRNA levels of collagen type I (COL1) alpha 1 (COL1A1), COL1 alpha 2 (COL1A2), elastin, matrix metalloproteinase 1 (MMP‐1), tissue inhibitor of metalloproteinase 1 (TIMP‐1), and TIMP‐2. Procollagen Type I C‐peptide (PIP) enzyme immunoassay (EIA) Kit assay was carried out to analyze procollagen production. Western Blot was employed to examine the effect of PLLA and transforming frown factor (TGF‐β) receptor‐specific inhibitor (SB431542) on protein levels of COL1A1 and TGF‐β/Smad signaling pathway related proteins.ResultsWith the increase of PLLA concentration, the production of procollagen gradually increased, and both protein and mRNA levels of COL1A1 and COL1A2 gradually increased (p < 0.001). Elevated PLLA concentrations increased elastin, TIMP‐1, and TIMP‐2 levels and attenuated MMP‐1 expression. PLLA increased TGF‐β levels in a dose‐dependently manner. p‐Smad2 and p‐Smad3 protein levels were also increased by PLLA, but the influences were reversed by SB431542 (p < 0.001). Similarly, increased levels of COL1A1, COL1A2, TIMP‐1, and TIMP‐2 caused by PLLA were significantly inhibited by SB431542, whereas MMP‐1 was typically elevated (p < 0.001).ConclusionPoly‐L‐Lactic Acid promotes the collagen production of dermal fibroblasts by activating the TGF‐β/Smad signaling pathway. The findings may lay a foundation for clinical material applications of PLLA.