An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices
Fibrosis can affect any organ, resulting in the loss of tissue architecture and function with often life-threatening consequences. Pathologically, fibrosis is characterised by the expansion of connective tissue due to excessive deposition of extracellular matrix (ECM) proteins, including the fibrill...
Gespeichert in:
| Hauptverfasser: | , , , , , , , , , , , , , , , , |
|---|---|
| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
July 1, 2021
|
| In: |
The European respiratory journal
Year: 2021, Jahrgang: 58, Heft: 1, Pages: 1-22 |
| ISSN: | 1399-3003 |
| DOI: | 10.1183/13993003.00221-2020 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1183/13993003.00221-2020 Verlag, lizenzpflichtig, Volltext: https://erj.ersjournals.com/content/58/1/2000221 
|
| Verfasserangaben: | Muzamil Majid Khan, Daniel Poeckel, Aliaksandr Halavatyi, Joanna Zukowska-Kasprzyk, Frank Stein, Johanna Vappiani, Daniel C. Sevin, Christian Tischer, Nico Zinn, Jessica D. Eley, Natasja Stæhr Gudmann, Thomas Muley, Hauke Winter, Andrew J. Fisher, Carmel B. Nanthakumar, Giovanna Bergamini and Rainer Pepperkok |
MARC
| LEADER | 00000caa a2200000 c 4500 | ||
|---|---|---|---|
| 001 | 1771034440 | ||
| 003 | DE-627 | ||
| 005 | 20220820044557.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 210920s2021 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1183/13993003.00221-2020 |2 doi | |
| 035 | |a (DE-627)1771034440 | ||
| 035 | |a (DE-599)KXP1771034440 | ||
| 035 | |a (OCoLC)1341421033 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rda | ||
| 041 | |a eng | ||
| 084 | |a 33 |2 sdnb | ||
| 100 | 1 | |a Khan, Muzamil Majid |e VerfasserIn |0 (DE-588)1107612608 |0 (DE-627)863546404 |0 (DE-576)475106385 |4 aut | |
| 245 | 1 | 3 | |a An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices |c Muzamil Majid Khan, Daniel Poeckel, Aliaksandr Halavatyi, Joanna Zukowska-Kasprzyk, Frank Stein, Johanna Vappiani, Daniel C. Sevin, Christian Tischer, Nico Zinn, Jessica D. Eley, Natasja Stæhr Gudmann, Thomas Muley, Hauke Winter, Andrew J. Fisher, Carmel B. Nanthakumar, Giovanna Bergamini and Rainer Pepperkok |
| 264 | 1 | |c July 1, 2021 | |
| 300 | |a 22 | ||
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Gesehen am 20.09.2021 | ||
| 520 | |a Fibrosis can affect any organ, resulting in the loss of tissue architecture and function with often life-threatening consequences. Pathologically, fibrosis is characterised by the expansion of connective tissue due to excessive deposition of extracellular matrix (ECM) proteins, including the fibrillar forms of collagen. A significant limitation for discovering cures for fibrosis is the availability of suitable human models and techniques to quantify mature fibrillar collagen deposition as close as possible to human physiological conditions. - Here we have extensively characterised an ex vivo cultured human lung tissue-derived, precision-cut lung slices (hPCLS) model using label-free second harmonic generation (SHG) light microscopy to quantify fibrillar collagen deposition and mass spectrometry-based techniques to obtain a proteomic and metabolomic fingerprint of hPCLS in ex vivo culture. - We demonstrate that hPCLS are viable and metabolically active, with mesenchymal, epithelial, endothelial and immune cell types surviving for at least 2 weeks in ex vivo culture. Analysis of hPCLS-conditioned supernatants showed a strong induction of pulmonary fibrosis-related ECM proteins upon transforming growth factor-β1 (TGF-β1) stimulation. This upregulation of ECM proteins was not translated into an increased deposition of fibrillar collagen. In support of this observation, we revealed the presence of a pro-ECM degradation activity in our ex vivo cultures of hPCLS, inhibition of which by a metalloproteinase inhibitor resulted in increased collagen deposition in response to TGF-β1 stimulation. - Together the data show that an integrated approach of measuring soluble pro-fibrotic markers alongside quantitative SHG-based analysis of fibrillar collagen is a valuable tool for studying pro-fibrotic signalling and testing anti-fibrotic agents. - Tweetable abstract ERSpublications - click to tweetMultiomic and label-free imaging-based characterisation of ex vivo cultured human precision-cut lung slices (hPCLS) reveals that MMP signalling is a rate-limiting factor necessary for deposition of fibrillar collagen in ECM of hPCLS https://bit.ly/3rcUa0e | ||
| 700 | 1 | |a Poeckel, Daniel |e VerfasserIn |4 aut | |
| 700 | 1 | |a Halavatyi, Aliaksandr |e VerfasserIn |0 (DE-588)1203389957 |0 (DE-627)168846980X |4 aut | |
| 700 | 1 | |a Zukowska-Kasprzyk, Joanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Stein, Frank |e VerfasserIn |4 aut | |
| 700 | 1 | |a Vappiani, Johanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Sevin, Daniel C. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Tischer, Christian |e VerfasserIn |4 aut | |
| 700 | 1 | |a Zinn, Nico |e VerfasserIn |4 aut | |
| 700 | 1 | |a Eley, Jessica D. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Gudmann, Natasja Stæhr |e VerfasserIn |4 aut | |
| 700 | 1 | |a Muley, Thomas |e VerfasserIn |0 (DE-588)1056885432 |0 (DE-627)794179169 |0 (DE-576)16759284X |4 aut | |
| 700 | 1 | |a Winter, Hauke |e VerfasserIn |0 (DE-588)1162076038 |0 (DE-627)1025509773 |0 (DE-576)176791531 |4 aut | |
| 700 | 1 | |a Fisher, Andrew J. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Nanthakumar, Carmel B. |e VerfasserIn |4 aut | |
| 700 | 1 | |a Bergamini, Giovanna |e VerfasserIn |4 aut | |
| 700 | 1 | |a Pepperkok, Rainer |e VerfasserIn |0 (DE-588)1150711302 |0 (DE-627)1010920588 |0 (DE-576)497195461 |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t The European respiratory journal |d Lausanne : ERS, 1988 |g 58(2021), 1, Artikel-ID 2000221, Seite 1-22 |h Online-Ressource |w (DE-627)306646803 |w (DE-600)1499101-9 |w (DE-576)091142504 |x 1399-3003 |7 nnas |a An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices |
| 773 | 1 | 8 | |g volume:58 |g year:2021 |g number:1 |g elocationid:2000221 |g pages:1-22 |g extent:22 |a An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices |
| 856 | 4 | 0 | |u https://doi.org/10.1183/13993003.00221-2020 |x Verlag |x Resolving-System |z lizenzpflichtig |3 Volltext |
| 856 | 4 | 0 | |u https://erj.ersjournals.com/content/58/1/2000221 |x Verlag |z lizenzpflichtig |3 Volltext |
| 951 | |a AR | ||
| 992 | |a 20210920 | ||
| 993 | |a Article | ||
| 994 | |a 2021 | ||
| 998 | |g 1150711302 |a Pepperkok, Rainer |m 1150711302:Pepperkok, Rainer |p 17 |y j | ||
| 998 | |g 1162076038 |a Winter, Hauke |m 1162076038:Winter, Hauke |d 910000 |d 950000 |d 950900 |d 50000 |e 910000PW1162076038 |e 950000PW1162076038 |e 950900PW1162076038 |e 50000PW1162076038 |k 0/910000/ |k 1/910000/950000/ |k 2/910000/950000/950900/ |k 0/50000/ |p 13 | ||
| 998 | |g 1056885432 |a Muley, Thomas |m 1056885432:Muley, Thomas |d 910000 |d 950000 |d 950900 |e 910000PM1056885432 |e 950000PM1056885432 |e 950900PM1056885432 |k 0/910000/ |k 1/910000/950000/ |k 2/910000/950000/950900/ |p 12 | ||
| 998 | |g 1203389957 |a Halavatyi, Aliaksandr |m 1203389957:Halavatyi, Aliaksandr |d 50000 |e 50000PH1203389957 |k 0/50000/ |p 3 | ||
| 999 | |a KXP-PPN1771034440 |e 397930812X | ||
| BIB | |a Y | ||
| SER | |a journal | ||
| JSO | |a {"language":["eng"],"name":{"displayForm":["Muzamil Majid Khan, Daniel Poeckel, Aliaksandr Halavatyi, Joanna Zukowska-Kasprzyk, Frank Stein, Johanna Vappiani, Daniel C. Sevin, Christian Tischer, Nico Zinn, Jessica D. Eley, Natasja Stæhr Gudmann, Thomas Muley, Hauke Winter, Andrew J. Fisher, Carmel B. Nanthakumar, Giovanna Bergamini and Rainer Pepperkok"]},"note":["Gesehen am 20.09.2021"],"person":[{"family":"Khan","role":"aut","display":"Khan, Muzamil Majid","given":"Muzamil Majid"},{"display":"Poeckel, Daniel","given":"Daniel","role":"aut","family":"Poeckel"},{"family":"Halavatyi","role":"aut","given":"Aliaksandr","display":"Halavatyi, Aliaksandr"},{"family":"Zukowska-Kasprzyk","role":"aut","display":"Zukowska-Kasprzyk, Joanna","given":"Joanna"},{"given":"Frank","display":"Stein, Frank","family":"Stein","role":"aut"},{"role":"aut","family":"Vappiani","given":"Johanna","display":"Vappiani, Johanna"},{"display":"Sevin, Daniel C.","given":"Daniel C.","family":"Sevin","role":"aut"},{"family":"Tischer","role":"aut","given":"Christian","display":"Tischer, Christian"},{"given":"Nico","display":"Zinn, Nico","family":"Zinn","role":"aut"},{"role":"aut","family":"Eley","display":"Eley, Jessica D.","given":"Jessica D."},{"display":"Gudmann, Natasja Stæhr","given":"Natasja Stæhr","family":"Gudmann","role":"aut"},{"given":"Thomas","display":"Muley, Thomas","family":"Muley","role":"aut"},{"role":"aut","family":"Winter","display":"Winter, Hauke","given":"Hauke"},{"display":"Fisher, Andrew J.","given":"Andrew J.","family":"Fisher","role":"aut"},{"role":"aut","family":"Nanthakumar","given":"Carmel B.","display":"Nanthakumar, Carmel B."},{"family":"Bergamini","role":"aut","display":"Bergamini, Giovanna","given":"Giovanna"},{"display":"Pepperkok, Rainer","given":"Rainer","family":"Pepperkok","role":"aut"}],"recId":"1771034440","physDesc":[{"extent":"22 S."}],"id":{"eki":["1771034440"],"doi":["10.1183/13993003.00221-2020"]},"title":[{"title":"An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices","title_sort":"integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slices"}],"type":{"bibl":"article-journal","media":"Online-Ressource"},"origin":[{"dateIssuedKey":"2021","dateIssuedDisp":"July 1, 2021"}],"relHost":[{"physDesc":[{"extent":"Online-Ressource"}],"id":{"eki":["306646803"],"issn":["1399-3003"],"zdb":["1499101-9"]},"title":[{"subtitle":"flagship scientific journal of ERS","title":"The European respiratory journal","title_sort":"European respiratory journal"}],"origin":[{"publisherPlace":"Lausanne ; Copenhagen","dateIssuedKey":"1988","dateIssuedDisp":"1988-","publisher":"ERS ; Munksgaard"}],"name":{"displayForm":["European Respiratory Society"]},"recId":"306646803","disp":"An integrated multiomic and quantitative label-free microscopy-based approach to study pro-fibrotic signalling in ex vivo human precision-cut lung slicesThe European respiratory journal","type":{"media":"Online-Ressource","bibl":"periodical"},"corporate":[{"role":"isb","display":"European Respiratory Society"}],"titleAlt":[{"title":"official journal of the European Society for Clinical Respiratory Physiology : ERJ"},{"title":"ERJ"}],"part":{"volume":"58","year":"2021","extent":"22","pages":"1-22","issue":"1","text":"58(2021), 1, Artikel-ID 2000221, Seite 1-22"},"language":["eng"],"note":["Gesehen am 25.04.2025","Fortsetzung der Druck-Ausgabe"],"pubHistory":["1.1988 -"]}]} | ||
| SRT | |a KHANMUZAMIINTEGRATED1202 | ||