Involvement of serum amyloid A1 in the rupture of fetal membranes through induction of collagen I degradation

The de novo synthesis of serum amyloid A1 (SAA1) is augmented in human fetal membranes at parturition. However, its role in parturitionremains largely unknown. Here, we investigated whether SAA1 wasinvolved inthe rupture of fetal membranes, a crucial event in parturition accompanied with extensive degradation of collagens. Results showed that SAA1 decreased both intracellular and extracellular COL1A1 and COL1A2 abundance,the two subunits ofcollagen I, without affecting theirmRNAlevels in human amnion fibroblasts.These reductions were completely blocked only with inhibition of both matrix metalloproteases (MMPs)and autophagy. Consistently,SAA1 increased MMP-2/9 abundance andthe markers for autophagic activation including autophagy related 7 and the microtubule-associated protein light chain 3 beta (LC3B) II/I ratiowith the formation of LC3punctas and autophagic vacuoles in the fibroblasts. Moreover,the autophagic degradation of COL1A1/COL1A2 and activation of MMP-2/9 by SAA1 wereblocked by inhibitors for the toll-like receptors 2/4 (TLR2/4) or NF-B. Finally, reciprocal corresponding changes of SAA1 and collagen I were observed in the amnion following spontaneous rupture of membranes at parturition. Conclusively, SAA1 may participate inmembrane ruptureat parturitionby degradating collagen I via both autophagicand MMP pathways. These effects of SAA1 appear to be mediated by the TLR2/4 receptors and the NF-B pathway.

Source: Clinical Science - January 25, 2019 Category: Biomedical Science Authors: Wang, W.-s., Li, W.-j., Wang, Y.-w., Wang, L.-y., Mi, Y.-b., Lu, J.-w., Lu, Y., Zhang, C.-y., Sun, K. Tags: PublishAheadOfPrint Source Type: research