# RNA-Seq of Gingival Fibroblasts Grown on Collagen Membranes and Hyaluronic Acid

**Authors:** Layla Panahipour, Xiaoyu Huang, Reinhard Gruber

PMC · DOI: 10.3390/jfb17020057 · 2026-01-23

## TL;DR

This study shows how different collagen membranes affect gene activity in gum fibroblasts, with collagen fleece having a stronger impact on extracellular matrix formation than other types.

## Contribution

The study reveals specific gene expression changes in fibroblasts on collagen membranes, highlighting differences between collagen fleece and mucoderm®.

## Key findings

- Collagen fleece upregulates extracellular matrix-related genes like CCN1, CCN2, and COL1A1 compared to mucoderm®.
- HA coating increases IL24 expression in mucoderm® but not in collagen fleece.
- Collagen membranes cause significant transcriptional changes, including upregulation of CEMIP and downregulation of ADM2.

## Abstract

Purpose: Collagen membranes are widely used biomaterials in periodontal and implant dentistry and can be combined with hyaluronic acid (HA). Although collagen membranes are expected to exhibit bioactive properties and support fibroblast infiltration, their specific impact on fibroblast behavior remains unclear. Methods: To investigate this, human gingival fibroblasts were seeded on collagen matrices—mucoderm®, a collagen fleece derived from dermis, and Jason® membrane derived from pericardium—with or without lyophilized HA. Subsequent bulk RNA sequencing was used to assess transcriptional responses. Results: Both mucoderm® and the collagen fleece caused significant transcriptional changes compared with fibroblasts grown on standard tissue culture surfaces and Jason® membrane. These changes included upregulation of CEMIP, STC1, and TM4SF1, and downregulation of ADM2, PSAT1, and GPR1. Notably, the collagen fleece increased expression of extracellular matrix-related genes including CCN1, CCN2, COL1A1, POSTN, SPARC, TAGLN, FBN2, CCDC80, and CREB3L1 relative to mucoderm®. Additionally, the expression of proteases MMP3 and MMP10, along with detoxification-related genes MT1E, MT2A, HMOX1, and NQO1, was relatively decreased. HA coating elevated IL24 expression in mucoderm®, but no similar effect was observed in the collagen fleece. Conclusions: These findings demonstrate that collagen membranes can influence the transcriptome of gingival fibroblasts and suggest that collagen fleece has a stronger effect on extracellular matrix formation than mucoderm®. Furthermore, HA coating does not consistently alter fibroblast responses.

## Linked entities

- **Genes:** CEMIP (cell migration inducing hyaluronidase 1) [NCBI Gene 57214], STC1 (stanniocalcin 1) [NCBI Gene 6781], TM4SF1 (transmembrane 4 L six family member 1) [NCBI Gene 4071], ADM2 (adrenomedullin 2) [NCBI Gene 79924], PSAT1 (phosphoserine aminotransferase 1) [NCBI Gene 29968], CMKLR2 (chemerin chemokine-like receptor 2) [NCBI Gene 2825], CCN1 (cellular communication network factor 1) [NCBI Gene 3491], CCN2 (cellular communication network factor 2) [NCBI Gene 1490], COL1A1 (collagen type I alpha 1 chain) [NCBI Gene 1277], POSTN (periostin) [NCBI Gene 10631], SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678], TAGLN (transgelin) [NCBI Gene 6876], FBN2 (fibrillin 2) [NCBI Gene 2201], CCDC80 (coiled-coil domain containing 80) [NCBI Gene 151887], CREB3L1 (cAMP responsive element binding protein 3 like 1) [NCBI Gene 90993], MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314], MMP10 (matrix metallopeptidase 10) [NCBI Gene 4319], MT1E (metallothionein 1E) [NCBI Gene 4493], MT2A (metallothionein 2A) [NCBI Gene 4502], HMOX1 (heme oxygenase 1) [NCBI Gene 3162], NQO1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 1728], IL24 (interleukin 24) [NCBI Gene 11009]
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** THBD (thrombomodulin) [NCBI Gene 7056] {aka AHUS6, BDCA-3, BDCA3, CD141, THPH12, THRM}, CXCL3 (C-X-C motif chemokine ligand 3) [NCBI Gene 2921] {aka CINC-2b, GRO3, GROg, MIP-2b, MIP2B, SCYB3}, PSAT1 (phosphoserine aminotransferase 1) [NCBI Gene 29968] {aka EPIP, NLS2, PSA, PSAT, PSATD}, DUSP5 (dual specificity phosphatase 5) [NCBI Gene 1847] {aka DUSP, HVH3}, MMP3 (matrix metallopeptidase 3) [NCBI Gene 4314] {aka CHDS6, MMP-3, SL-1, STMY, STMY1, STR1}, HSPA1A (heat shock protein family A (Hsp70) member 1A) [NCBI Gene 3303] {aka HEL-S-103, HSP70, HSP70-1, HSP70-1A, HSP70-2, HSP70.1}, CCN1 (cellular communication network factor 1) [NCBI Gene 3491] {aka CYR61, GIG1, IBP-10, IGFBP-10, IGFBP10}, TFPI2 (tissue factor pathway inhibitor 2) [NCBI Gene 7980] {aka PP5, REF1, TFPI-2}, PHGDH (phosphoglycerate dehydrogenase) [NCBI Gene 26227] {aka 3-PGDH, 3PGDH, HEL-S-113, NLS, NLS1, PDG}, PCK2 (phosphoenolpyruvate carboxykinase 2, mitochondrial) [NCBI Gene 5106] {aka PEPCK, PEPCK-M, PEPCK2, mtPCK2}, NQO1 (NAD(P)H quinone dehydrogenase 1) [NCBI Gene 1728] {aka DHQU, DIA4, DTD, NMOR1, NMORI, QR1}, LOXL1 (lysyl oxidase like 1) [NCBI Gene 4016] {aka LOL, LOXL}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, MT2A (metallothionein 2A) [NCBI Gene 4502] {aka MT-2, MT-II, MT2}, MTHFD2 (methylenetetrahydrofolate dehydrogenase (NADP+ dependent) 2, methenyltetrahydrofolate cyclohydrolase) [NCBI Gene 10797] {aka NMDMC}, MT1X (metallothionein 1X) [NCBI Gene 4501] {aka MT-1l, MT1}, ADM2 (adrenomedullin 2) [NCBI Gene 79924] {aka AM2, dJ579N16.4}, CEMIP (cell migration inducing hyaluronidase 1) [NCBI Gene 57214] {aka CCSP1, CEMIP1, HYBID, KIAA1199, TMEM2L}, PTGS2 (prostaglandin-endoperoxide synthase 2) [NCBI Gene 5743] {aka COX-2, COX2, GRIPGHS, PGG/HS, PGHS-2, PHS-2}, DPT (dermatopontin) [NCBI Gene 1805] {aka TRAMP}, COL6A3 (collagen type VI alpha 3 chain) [NCBI Gene 1293] {aka BTHLM1, BTHLM1C, DYT27, UCMD1, UCMD1C}, EPHB2 (EPH receptor B2) [NCBI Gene 2048] {aka BDPLT22, CAPB, DRT, EK5, EPHT3, ERK}, ABHD17C (abhydrolase domain containing 17C, depalmitoylase) [NCBI Gene 58489] {aka FAM108C1}, LIF (LIF interleukin 6 family cytokine) [NCBI Gene 3976] {aka CDF, DIA, HILDA, MLPLI}, ARID5A (AT-rich interaction domain 5A) [NCBI Gene 10865] {aka MRF-1, MRF1, RP11-363D14}, PTGES (prostaglandin E synthase) [NCBI Gene 9536] {aka MGST-IV, MGST1-L1, MGST1L1, MPGES, PGES, PIG12}, IER3 (immediate early response 3) [NCBI Gene 8870] {aka DIF-2, DIF2, GLY96, IEX-1, IEX-1L, IEX1}, PTHLH (parathyroid hormone like hormone) [NCBI Gene 5744] {aka BDE2, HHM, PLP, PTHR, PTHRP}, GRPEL1 (GrpE like 1, mitochondrial) [NCBI Gene 80273] {aka GrpE, HMGE, mt-GrpE#1}, GCLM (glutamate-cysteine ligase modifier subunit) [NCBI Gene 2730] {aka GLCLR}, COX2 (cytochrome c oxidase subunit II) [NCBI Gene 4513] {aka COII, MTCO2}, SPHK1 (sphingosine kinase 1) [NCBI Gene 8877] {aka SPHK}, FBN2 (fibrillin 2) [NCBI Gene 2201] {aka CCA, DA9, EOMD}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, CCNA2 (cyclin A2) [NCBI Gene 890] {aka CCN1, CCNA}, ABCC4 (ATP binding cassette subfamily C member 4 (PEL blood group)) [NCBI Gene 10257] {aka MOAT-B, MOATB, MRP4}, ICAM1 (intercellular adhesion molecule 1) [NCBI Gene 3383] {aka BB2, CD54, P3.58}, TPX2 (TPX2 microtubule nucleation factor) [NCBI Gene 22974] {aka C20orf1, C20orf2, DIL-2, DIL2, FLS353, GD:C20orf1}, CABLES1 (Cdk5 and Abl enzyme substrate 1) [NCBI Gene 91768] {aka CABL1, CABLES, HsT2563, IK3-1}, PTX3 (pentraxin 3) [NCBI Gene 5806] {aka TNFAIP5, TSG-14}, MXRA5 (matrix remodeling associated 5) [NCBI Gene 25878], CEBPG (CCAAT enhancer binding protein gamma) [NCBI Gene 1054] {aka GPE1BP, IG/EBP-1}, CREB3L1 (cAMP responsive element binding protein 3 like 1) [NCBI Gene 90993] {aka C16DELp11.2, DEL16p11.2, OASIS, OI16}, NID2 (nidogen 2) [NCBI Gene 22795] {aka NID-2}, SREBF1 (sterol regulatory element binding transcription factor 1) [NCBI Gene 6720] {aka HMD, IFAP2, SREBP1, bHLHd1}, PRSS35 (serine protease 35) [NCBI Gene 167681] {aka C6orf158, dJ223E3.1}, MMP1 (matrix metallopeptidase 1) [NCBI Gene 4312] {aka CLG}, ALDH1L2 (aldehyde dehydrogenase 1 family member L2) [NCBI Gene 160428] {aka mtFDH}, TRIB3 (tribbles pseudokinase 3) [NCBI Gene 57761] {aka C20orf97, NIPK, SINK, SKIP3, TRB3}, IL33 (interleukin 33) [NCBI Gene 90865] {aka C9orf26, DVS27, IL1F11, NF-HEV, NFEHEV}, NR4A3 (nuclear receptor subfamily 4 group A member 3) [NCBI Gene 8013] {aka CHN, CSMF, MINOR, NOR1}, IL1R1 (interleukin 1 receptor type 1) [NCBI Gene 3554] {aka CD121A, CRMO3, D2S1473, IL-1R-alpha, IL-1RT1, IL1R}, MEDAG (mesenteric estrogen dependent adipogenesis) [NCBI Gene 84935] {aka AWMS3, C13orf33, MEDA-4, MEDA4, hAWMS3}, CCN2 (cellular communication network factor 2) [NCBI Gene 1490] {aka CTGF, HCS24, IBP-8, IGFBP8, KMD, NOV2}, SPARC (secreted protein acidic and cysteine rich) [NCBI Gene 6678] {aka BM-40, OI17, ON, ONT}, CYGB (cytoglobin) [NCBI Gene 114757] {aka HGB, NOD, STAP}, HSPA1B (heat shock protein family A (Hsp70) member 1B) [NCBI Gene 3304] {aka HSP70-1, HSP70-1B, HSP70-2, HSP70.1, HSP70.2, HSP72}, POSTN (periostin) [NCBI Gene 10631] {aka OSF-2, OSF2, PDLPOSTN, PN}, COL5A1 (collagen type V alpha 1 chain) [NCBI Gene 1289] {aka EDSC, EDSCL1, FMDMF}, PTGS1 (prostaglandin-endoperoxide synthase 1) [NCBI Gene 5742] {aka COX1, COX3, PCOX1, PES-1, PGG/HS, PGHS-1}
- **Diseases:** osteosarcoma (MESH:D012516), inflammatory (MESH:D007249), injury to (MESH:D014947), TCS (MESH:D010534), carcinoma (MESH:D009369), diabetic (MESH:D003920), bleeding (MESH:D006470), hypoxia (MESH:D000860), osteoarthritis (MESH:D010003), implantitis (MESH:D057873), heme (MESH:D046351), meniscus (MESH:D000070600)
- **Chemicals:** zinc (MESH:D015032), carbon (MESH:D002244), polysaccharide (MESH:D011134), prostaglandin (MESH:D011453), aldehydes (MESH:D000447), HA (MESH:D006820), DMEM (-), L-serine (MESH:D012694), polycaprolactone (MESH:C016240), titanium (MESH:D014025), lipid (MESH:D008055), heavy metals (MESH:D019216), cadmium (MESH:D002104)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12942325/full.md

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Source: https://tomesphere.com/paper/PMC12942325