PMID- 36548206 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20230308 IS - 1873-149X (Electronic) IS - 0928-4680 (Print) IS - 0928-4680 (Linking) VI - 29 IP - 4 DP - 2022 Nov 23 TI - The Effect of TGFbeta1 in Adipocyte on Inflammatory and Fibrotic Markers at Different Stages of Adipocyte Differentiation. PG - 640-649 LID - 10.3390/pathophysiology29040050 [doi] AB - Transforming growth factor beta (TGFbeta) is a versatile cytokine. Although a profibrotic role of TGFbeta is well established, its effect on tissue inhibitor of metalloproteinase (TIMPs) and inflammatory mediators are incompletely described. This study investigates the profibrotic and pro-inflammatory role of TGFbeta1 during adipocyte differentiation. NIH3T3L1 cells were used for the in vitro study and were differentiated by adding a standard differentiation mix either with rosiglitazone (R-Diff) or without (S-Diff). Recombinant TGFbeta1 (2 ng/mL) was added to the undifferentiated preadipocyte during the commitment stage and at the terminal differentiation stage. TGFbeta1 treatment significantly decreased adiponectin mRNA at both early commitment (>300 fold) and terminal differentiated cells [S-Diff (~33%) or R-Diff (~20%)]. TGFbeta1 upregulated collagen VI mRNA and its regulators connective tissue growth factor (CCN2/CTGF), TIMP1 and TIMP3 mRNA levels in undifferentiated preadipocytes and adipocytes at commitment stage. But in the terminal differentiated adipocytes, changes in mRNA and protein of collagen VI and TIMP3 mRNA were not observed despite an increase in CCN2/CTGF, TIMP1 mRNA. Although TGFbeta1 upregulated interleukin-6 (IL6) and monocyte chemoattractant protein-1 (MCP1) mRNA at all stages of differentiation, decreased tumor necrosis factor-alpha (TNFalpha) mRNA was observed early in adipocyte differentiation. This study highlights the complex role of TGFbeta1 on extracellular matrix (ECM) remodeling and inflammatory markers in stimulating both synthetic and inhibitory markers of fibrosis at different stages of adipocyte differentiation. FAU - Maharjan, Babu Raja AU - Maharjan BR AD - Greg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. AD - School of Medicine, Department of Biochemistry, Patan Academy of Health Sciences, Lalitpur 44700, Nepal. FAU - McLennan, Susan V AU - McLennan SV AD - Greg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. AD - New South Wales Health Pathology, Sydney, NSW 2050, Australia. FAU - Twigg, Stephen M AU - Twigg SM AD - Greg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. AD - Department of Endocrinology, Royal Prince Alfred Hospital, Sydney, NSW 2006, Australia. FAU - Williams, Paul F AU - Williams PF AUID- ORCID: 0000-0002-8654-1697 AD - Greg Brown Diabetes & Endocrinology Laboratory, Sydney Medical School, University of Sydney, Sydney, NSW 2006, Australia. LA - eng GR - Australia Award/Government of Australia/ GR - Kellion Diabetes Fund in the Sydney Medical School Foundation/The University of Sydney/ GR - Endocrinology Trust Fund/Royal Prince Alfred Hospital Sydney/ PT - Journal Article DEP - 20221123 PL - Switzerland TA - Pathophysiology JT - Pathophysiology : the official journal of the International Society for Pathophysiology JID - 9433813 PMC - PMC9788619 OTO - NOTNLM OT - TGFbeta OT - adipocyte OT - fibrosis OT - inflammation OT - stages of differentiation COIS- The authors declare no conflict of interest. EDAT- 2022/12/23 06:00 MHDA- 2022/12/23 06:01 PMCR- 2022/11/23 CRDT- 2022/12/22 13:12 PHST- 2022/10/20 00:00 [received] PHST- 2022/11/18 00:00 [revised] PHST- 2022/11/21 00:00 [accepted] PHST- 2022/12/22 13:12 [entrez] PHST- 2022/12/23 06:00 [pubmed] PHST- 2022/12/23 06:01 [medline] PHST- 2022/11/23 00:00 [pmc-release] AID - pathophysiology29040050 [pii] AID - pathophysiology-29-00050 [pii] AID - 10.3390/pathophysiology29040050 [doi] PST - epublish SO - Pathophysiology. 2022 Nov 23;29(4):640-649. doi: 10.3390/pathophysiology29040050.