{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:67633"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:67633","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"The role of relaxin in the regulation of human liver and kidney fibrosis","abstract":"Liver fibrosis has a range of aetiologies and is a global cause of mortality. A
critical effect of liver fibrosis which also increases mortality is portal
hypertension. The hepatic stellate cell is accepted as a major progenitor of liver
myofibroblasts, which have been shown to be a major source of collagen and
extracellular matrix proteins that disrupt liver architecture and function. Relaxin
is a hormone involved in remodelling of extracellular matrix in the uterus and
cervix and is known to increase renal blood flow in pregnancy. It has been
implicated in the regulation of fibrosis in animal models and to modify the cell
biology of hepatic stellate cells in vitro. I have demonstrated the profile of
expression of relaxin receptors in primary human stellate cells (HSC), showing
them to express RXFP-1, 3 and 4. Using a cAMP assay I confirm these receptors
to be functional, with RXFP-1 positively and RXFP-3 and 4 negatively coupling
to cAMP. The expression of RXFP-1 is coupled with the level of activation,
demonstrating a possible role for H2-relaxin in the regulation of HSC. I have
established a dynamic regulation of fibrotic mediators and HSC activation
markers, including a reduction in ?-SMA, TIMP-1 and TGF-? with increases in
MMP-1 and MMP-2, consistent with H2-relaxin having potentially therapeutic
antifibrotic effects by increasing the fibrolytic phenotype. In addition through
the use of gel contraction assays I demonstrate that H2-relaxin reduces serum or
endothelin-1 induced HSC contraction. Through the use of siRNA I have
confirmed that H2-relaxin mediates its regulation of fibrotic mediators and HSC
activation markers as well as the inhibition of gel contraction through the relaxin
receptor RXFP-1. I have evidence to suggest that the inhibition of contraction
may in part be via nitric oxide release in HSC. In conclusion I propose that
RXFP-1 is a potential therapeutic target in end stage human liver disease,
targeting fibrosis and portal blood hypertension via both resolution of the
phenotypic collagen deposition and vascular constriction associated with the
human hepatic stellate cell.","abstract_html":"Liver fibrosis has a range of aetiologies and is a global cause of mortality. A<br/>critical effect of liver fibrosis which also increases mortality is portal<br/>hypertension. The hepatic stellate cell is accepted as a major progenitor of liver<br/>myofibroblasts, which have been shown to be a major source of collagen and<br/>extracellular matrix proteins that disrupt liver architecture and function. Relaxin<br/>is a hormone involved in remodelling of extracellular matrix in the uterus and<br/>cervix and is known to increase renal blood flow in pregnancy. It has been<br/>implicated in the regulation of fibrosis in animal models and to modify the cell<br/>biology of hepatic stellate cells in vitro. I have demonstrated the profile of<br/>expression of relaxin receptors in primary human stellate cells (HSC), showing<br/>them to express RXFP-1, 3 and 4. Using a cAMP assay I confirm these receptors<br/>to be functional, with RXFP-1 positively and RXFP-3 and 4 negatively coupling<br/>to cAMP. The expression of RXFP-1 is coupled with the level of activation,<br/>demonstrating a possible role for H2-relaxin in the regulation of HSC. I have<br/>established a dynamic regulation of fibrotic mediators and HSC activation<br/>markers, including a reduction in ?-SMA, TIMP-1 and TGF-? with increases in<br/>MMP-1 and MMP-2, consistent with H2-relaxin having potentially therapeutic<br/>antifibrotic effects by increasing the fibrolytic phenotype. In addition through<br/>the use of gel contraction assays I demonstrate that H2-relaxin reduces serum or<br/>endothelin-1 induced HSC contraction. Through the use of siRNA I have<br/>confirmed that H2-relaxin mediates its regulation of fibrotic mediators and HSC<br/>activation markers as well as the inhibition of gel contraction through the relaxin<br/>receptor RXFP-1. I have evidence to suggest that the inhibition of contraction<br/>may in part be via nitric oxide release in HSC. In conclusion I propose that<br/>RXFP-1 is a potential therapeutic target in end stage human liver disease,<br/>targeting fibrosis and portal blood hypertension via both resolution of the<br/>phenotypic collagen deposition and vascular constriction associated with the<br/>human hepatic stellate cell.","abstract_has_math":false,"creators":["Hayden, Annette Louise"],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Collins, J.E.","Princivalle, M.","Iredale, J.P."],"committee_chairs":[],"committee_members":[],"year":2009,"date_issued":"2009-04","date_published":"2009-04","updated_at":"2026-07-24T04:36:06Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Collins, J.E.","Princivalle, M.","Iredale, J.P."]},{"key":"dc:creator","label":"Author","values":["Hayden, Annette Louise"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2009-04"]},{"key":"dc:date.issued","label":"Date","values":["2009-04"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Infection Inflammation & Immunity (pre 2011 reorg)","School of Medicine"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/67633/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/67633/1/Annette_Thesis_Final_Version.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Liver fibrosis has a range of aetiologies and is a global cause of mortality. A
critical effect of liver fibrosis which also increases mortality is portal
hypertension. The hepatic stellate cell is accepted as a major progenitor of liver
myofibroblasts, which have been shown to be a major source of collagen and
extracellular matrix proteins that disrupt liver architecture and function. Relaxin
is a hormone involved in remodelling of extracellular matrix in the uterus and
cervix and is known to increase renal blood flow in pregnancy. It has been
implicated in the regulation of fibrosis in animal models and to modify the cell
biology of hepatic stellate cells in vitro. I have demonstrated the profile of
expression of relaxin receptors in primary human stellate cells (HSC), showing
them to express RXFP-1, 3 and 4. Using a cAMP assay I confirm these receptors
to be functional, with RXFP-1 positively and RXFP-3 and 4 negatively coupling
to cAMP. The expression of RXFP-1 is coupled with the level of activation,
demonstrating a possible role for H2-relaxin in the regulation of HSC. I have
established a dynamic regulation of fibrotic mediators and HSC activation
markers, including a reduction in ?-SMA, TIMP-1 and TGF-? with increases in
MMP-1 and MMP-2, consistent with H2-relaxin having potentially therapeutic
antifibrotic effects by increasing the fibrolytic phenotype. In addition through
the use of gel contraction assays I demonstrate that H2-relaxin reduces serum or
endothelin-1 induced HSC contraction. Through the use of siRNA I have
confirmed that H2-relaxin mediates its regulation of fibrotic mediators and HSC
activation markers as well as the inhibition of gel contraction through the relaxin
receptor RXFP-1. I have evidence to suggest that the inhibition of contraction
may in part be via nitric oxide release in HSC. In conclusion I propose that
RXFP-1 is a potential therapeutic target in end stage human liver disease,
targeting fibrosis and portal blood hypertension via both resolution of the
phenotypic collagen deposition and vascular constriction associated with the
human hepatic stellate cell."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["The role of relaxin in the regulation of human liver and kidney fibrosis"]}]}],"canonical_facts":{"dc:contributor.advisor":["Collins, J.E.","Princivalle, M.","Iredale, J.P."],"dc:creator":["Hayden, Annette Louise"],"dc:date":["2009-04"],"dc:date.issued":["2009-04"],"dc:description.abstract":["Liver fibrosis has a range of aetiologies and is a global cause of mortality. A
critical effect of liver fibrosis which also increases mortality is portal
hypertension. The hepatic stellate cell is accepted as a major progenitor of liver
myofibroblasts, which have been shown to be a major source of collagen and
extracellular matrix proteins that disrupt liver architecture and function. Relaxin
is a hormone involved in remodelling of extracellular matrix in the uterus and
cervix and is known to increase renal blood flow in pregnancy. It has been
implicated in the regulation of fibrosis in animal models and to modify the cell
biology of hepatic stellate cells in vitro. I have demonstrated the profile of
expression of relaxin receptors in primary human stellate cells (HSC), showing
them to express RXFP-1, 3 and 4. Using a cAMP assay I confirm these receptors
to be functional, with RXFP-1 positively and RXFP-3 and 4 negatively coupling
to cAMP. The expression of RXFP-1 is coupled with the level of activation,
demonstrating a possible role for H2-relaxin in the regulation of HSC. I have
established a dynamic regulation of fibrotic mediators and HSC activation
markers, including a reduction in ?-SMA, TIMP-1 and TGF-? with increases in
MMP-1 and MMP-2, consistent with H2-relaxin having potentially therapeutic
antifibrotic effects by increasing the fibrolytic phenotype. In addition through
the use of gel contraction assays I demonstrate that H2-relaxin reduces serum or
endothelin-1 induced HSC contraction. Through the use of siRNA I have
confirmed that H2-relaxin mediates its regulation of fibrotic mediators and HSC
activation markers as well as the inhibition of gel contraction through the relaxin
receptor RXFP-1. I have evidence to suggest that the inhibition of contraction
may in part be via nitric oxide release in HSC. In conclusion I propose that
RXFP-1 is a potential therapeutic target in end stage human liver disease,
targeting fibrosis and portal blood hypertension via both resolution of the
phenotypic collagen deposition and vascular constriction associated with the
human hepatic stellate cell."],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/67633/1/Annette_Thesis_Final_Version.pdf"],"dc:publisher.department":["Infection Inflammation & Immunity (pre 2011 reorg)","School of Medicine"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/67633/"],"dc:title":["The role of relaxin in the regulation of human liver and kidney fibrosis"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:06Z"}