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Hypertrophic scar (HS) is one of the most common sequelae of patients, especially after burns and trauma. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating HS remain underexplored. Human hypertrophic scar-derived fibroblasts (HSFBs) have been shown to exert more potent promoting effects on extracellular matrix (ECM) accumulation than normal skin-derived fibroblasts (NSFBs) and are associated with enhanced HS formation. The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms. LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA (HSFAS). HSFAS overexpression significantly induces fibroblast proliferation, migration, and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs, while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation, migration, and myofibroblast trans-differentiation of HSFBs. Mechanistically, HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8). ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation, migration, myofibroblast trans-differentiation and apoptosis. Thus, our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function. Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.

Objective To investigate the role of lncRNA SNHG1 in homocysteine-induced pyroptosis of podocyte. Methods Cbs*+ mice were randomly divided into two groups : a normal diet group (ND) and a high methionine diet group (HMD). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocytes were cultured in vitro, and then assigned into a control group (Control, 0 imol/L Hcy) and a homocysteine intervention group (Hcy, 80 imol/L Hcy). Western blotting was used to detect the protein expression levels of Caspase-1, Cleaved Caspase-1, and NLRP3. Mouse renal glomerular podocyion group (OE-NC + Hey) and the lncSNHGl overexpression + homocysteine intervention group (OE-SNHG1 + Hcy) were also established.After 48 hours of intervention, Real-time fluorescence quantitative PCR was used to detect the expression of lncSNHGl in podocytes after Hcy intervention. Western blot was used to detect the expressions of Caspase-1, Cleaved Caspase-3 and NLRP3. Immunofluorescence was used to detect the expression levels of GSDMD and GSDMD-N. ELISA was used to detect the contents of IL-1p and IL-18. Results (l)ln the animal experiments, the expression levels of pyroptosis-related proteins Caspase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were all increased in the HMD group compared with the ND group. (2) In the cellular experiments, the expression levels of Caspase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were all increased in the Hcy group compared with the Control group, and the contents of pyroptosis-mediated inflammatory factors IL-1p and IL-18 were increased as well. (3) In the cellular experiments, the expression of lncSNHG1 was increased in the Hcy group compared with the control group. After transduction with lnc-SNHG1 lentivirus, the expression of lncSNHG1 was increased in the OE-SNHG1 group, compared with the control group and the OE-NC group. ( 4) In the cellular experiments, the expressions of pyroptosis-related proteins Cas-pase-1, Cleaved Caspase-1, NLRP3, GSDMD, and GSDMD-N were increased compared with the OE-NC+Hcy group, and the contents of pyroptosis-mediated inflammatory factors IL-1p and IL-18 were increased in the OE-SNHG1+Hcy group. Conclusion These results indicate that lncSNHG1 may play a role in promoting Hcy induced podocytepyroptosis. [ABSTRACT FROM AUTHOR]

Hypertrophic scar (HS) is one of the most common sequelae of patients, especially after burns and trauma. The roles of regulatory long noncoding RNAs (lncRNAs) in mediating HS remain underexplored. Human hypertrophic scar-derived fibroblasts (HSFBs) have been shown to exert more potent promoting effects on extracellular matrix (ECM) accumulation than normal skin-derived fibroblasts (NSFBs) and are associated with enhanced HS formation. The purpose of this study is to search for lncRNAs enriched in HSFBs and investigate their roles and mechanisms. LncRNA MSTRG.59347.16 is one of the most highly expressed lncRNAs in HS detected by lncRNA-seq and qRT-PCR and named as hypertrophic scar fibroblast-associated lncRNA (HSFAS). HSFAS overexpression significantly induces fibroblast proliferation, migration, and myofibroblast trans-differentiation and inhibits apoptosis in HSFBs, while knockdown of HSFAS results in augmented apoptosis and attenuated proliferation, migration, and myofibroblast trans-differentiation of HSFBs. Mechanistically, HSFAS suppresses the expression of A disintegrin and metalloproteinase with thrombospondin motifs 8 (ADAMTS8). ADAMTS8 knockdown rescues downregulated HSFAS-mediated fibroblast proliferation, migration, myofibroblast trans-differentiation and apoptosis. Thus, our findings uncover a previously unknown lncRNA-dependent regulatory pathway for fibroblast function. Targeted intervention in the HSFAS-ADAMTS8 pathway is a potential therapy for HS.