本研究旨在克隆山羊趋化因子(C-C基序)受体2(chemokine(C C motif)receptor-like 2,CCRL2)基因序列,并研究其组织和时序表达谱。以简州大耳羊为试验材料,应用RT-PCR方法克隆CCRL2基因并进行生物信息学分析,qPCR方法构建该基因在山羊不...本研究旨在克隆山羊趋化因子(C-C基序)受体2(chemokine(C C motif)receptor-like 2,CCRL2)基因序列,并研究其组织和时序表达谱。以简州大耳羊为试验材料,应用RT-PCR方法克隆CCRL2基因并进行生物信息学分析,qPCR方法构建该基因在山羊不同组织表达谱和不同月龄背最长肌、股二头肌和臂三头肌中的表达水平,并将基因表达与IMF含量进行相关分析。结果显示:克隆得到山羊CCRL2基因(GenBank登录号:KT165378)长度为1 143bp,编码区长度为1 047bp;qPCR分析表明,CCRL2mRNA在24月龄山羊心、肝、脾、肺、肾、脂肪、背最长肌、股二头肌和臂三头肌中均有不同程度的表达,其中脾表达量最高(P<0.01);时序表达中,CCRL2基因在股二头肌和臂三头肌中的表达量均在8~10月龄极显著高于1~3和24月龄(P<0.01),在背最长肌中则为24月龄极显著高于1~3和8~10月龄(P<0.01);相关分析显示,股二头肌中CCRL2基因mRNA表达量与IMF含量呈极显著负相关(P<0.01)。CCRL2基因可能参与山羊IMF沉积作用。展开更多
Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including ...Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6,ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients. CCRL2, a presumed member of the atypical chemokine receptor family, plays a key role in lung dendritic cell trafficking to peripheral lymph nodes.Recent studies have reported the expression of CCRL2 in different human cancer cell lines and tissues. However, its function and expression in prostate cancer has not been previously addressed.展开更多
The regenerative capacities of organs in adult mammals vary significantly.Unlike the liver,which possesses remarkable regenerative potential,the repair of cardiac injuries has long posed a critical medical challenge.R...The regenerative capacities of organs in adult mammals vary significantly.Unlike the liver,which possesses remarkable regenerative potential,the repair of cardiac injuries has long posed a critical medical challenge.Recent studies have highlighted the pivotal role of the immune microenvironment in repairing damage in these tissues,but the key cell types and their mechanisms of action remain incompletely understood.In this study,we established a model of concurrent physical trauma to the hearts and livers of adult mice,revealing that these two injured tissues drive distinct immune microenvironments.The liver primarily accumulates lymphocytes,whereas the heart recruits macrophages and neutrophils.Notably,CD160^(+)CD8^(+)intraepithelial lymphocytes in the liver were found to suppress fibrosis postliver injury and mitigate cardiac fibrosis when delivered via hydrogel patches.Conversely,in response to heart trauma,recruited inflammatory macrophages not only express proinflammatory cytokines but also coexpress CCRL2.While CCRL2 did not directly alter the intensity of the inflammatory response,it facilitated fibroblast proliferation and migration through its interaction with Na^(+)/K^(+)-ATPase on fibroblasts.These findings elucidated the contrasting immune microenvironments between the heart and liver following injury and provided novel insights and strategies for diagnosing and treating cardiac diseases.展开更多
Obesity-induced inflammation,characterized by augmented infiltration and altered balance of macrophages,is a critical component of systemic insulin resistance.Chemokine-chemokine receptor system plays a vital role in ...Obesity-induced inflammation,characterized by augmented infiltration and altered balance of macrophages,is a critical component of systemic insulin resistance.Chemokine-chemokine receptor system plays a vital role in the macrophages accumulation.CC-Chemokine Receptor-like 2(Ccrl2)is one of the receptors of Chemerin,which is a member of atypical chemokine receptors(ACKR)family,reported taking part in host immune responses and inflammation-related conditions.In our study,we found ccrl2 expression significantly elevated in visceral adipose tissue(VAT)of high fat diet(HFD)induced obese mice and ob/ob mice.Systemic deletion of Ccrl2 gene aggravated HFD induced obesity and insulin resistance and ccrl2−/−mice showed aggravated VAT inflammation and increased M1/M2 macrophages ratio,which is due to the increase of macrophages chemotaxis in Ccrl2 deficiency mice.Cumulatively,these results indicate that Ccrl2 has a critical function in obesity and obesity-induced insulin resistance via mediating macrophages chemotaxis.展开更多
文摘Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6,ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients. CCRL2, a presumed member of the atypical chemokine receptor family, plays a key role in lung dendritic cell trafficking to peripheral lymph nodes.Recent studies have reported the expression of CCRL2 in different human cancer cell lines and tissues. However, its function and expression in prostate cancer has not been previously addressed.
基金supported by the National Key Research and Development Program of China(2025YFA1309100)the distinguished Young Scientist Fund of NSFC(82125016)+6 种基金the National Natural Science Foundation of China Key Program(82230061)supported by the National Natural Science Foundation of China,Special Program(82341216)the Zhejiang Provincial Natural Science Foundation of China(LHDMD22H100002)supported by the National Key Research and Development Program of China(2021YFA1101803 and 2021ZD0203304)supported by the Jiangsu Science and Technology Project(Social Development)(BE2019669)the National Natural Science Foundation of China(82071046,82100540)supported by the 111 Program(D20036).
文摘The regenerative capacities of organs in adult mammals vary significantly.Unlike the liver,which possesses remarkable regenerative potential,the repair of cardiac injuries has long posed a critical medical challenge.Recent studies have highlighted the pivotal role of the immune microenvironment in repairing damage in these tissues,but the key cell types and their mechanisms of action remain incompletely understood.In this study,we established a model of concurrent physical trauma to the hearts and livers of adult mice,revealing that these two injured tissues drive distinct immune microenvironments.The liver primarily accumulates lymphocytes,whereas the heart recruits macrophages and neutrophils.Notably,CD160^(+)CD8^(+)intraepithelial lymphocytes in the liver were found to suppress fibrosis postliver injury and mitigate cardiac fibrosis when delivered via hydrogel patches.Conversely,in response to heart trauma,recruited inflammatory macrophages not only express proinflammatory cytokines but also coexpress CCRL2.While CCRL2 did not directly alter the intensity of the inflammatory response,it facilitated fibroblast proliferation and migration through its interaction with Na^(+)/K^(+)-ATPase on fibroblasts.These findings elucidated the contrasting immune microenvironments between the heart and liver following injury and provided novel insights and strategies for diagnosing and treating cardiac diseases.
基金This work was supported by National Key R&D Program of China(No.2018YFA0800401 to X.Li)National Natural Science Foundation of China(No.81770861 and 31571401 to X.Li)+1 种基金Chongqing Science and Technology Foundation(No.cstc2018jcyjAX0232)Science and Technology Research Program of Chongqing Municipal Education Commission(No.KJZD-K201800402).
文摘Obesity-induced inflammation,characterized by augmented infiltration and altered balance of macrophages,is a critical component of systemic insulin resistance.Chemokine-chemokine receptor system plays a vital role in the macrophages accumulation.CC-Chemokine Receptor-like 2(Ccrl2)is one of the receptors of Chemerin,which is a member of atypical chemokine receptors(ACKR)family,reported taking part in host immune responses and inflammation-related conditions.In our study,we found ccrl2 expression significantly elevated in visceral adipose tissue(VAT)of high fat diet(HFD)induced obese mice and ob/ob mice.Systemic deletion of Ccrl2 gene aggravated HFD induced obesity and insulin resistance and ccrl2−/−mice showed aggravated VAT inflammation and increased M1/M2 macrophages ratio,which is due to the increase of macrophages chemotaxis in Ccrl2 deficiency mice.Cumulatively,these results indicate that Ccrl2 has a critical function in obesity and obesity-induced insulin resistance via mediating macrophages chemotaxis.
