The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis ...The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.展开更多
Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2...Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.展开更多
基金the General Financial Grant from the China Postdoctoral Science Foundation(No.2014M560722)the Natural Science Foundation of Sichuan University of Science and Engineering(No.2015RC30)the Science and Technology Support Program of Sichuan Province of China(No.2017RZ0083).
文摘The abnormal growth of epithelium-like cells has been noticed in spontaneously hypertensive rats(SHRs)with hypertensive nephropathy.However,the characteristics of abnormal epithelium-like cells and their pathogenesis in hypertensive nephropathy are not fully understood.In the present study,we investigated the correlation of epithelium-like cells with glomerular injury,and the effects of early drug intervention with telmisartan,an anti-hypertensive drug,on the growth of epithelium-like cells.The results showed that the epithelium-like cells were obviously observed lining along the luminal surface of Bowman’s capsule in glomeruli,significantly resulting in the atrophy of the glomerular tuft.Some of the epithelium-like cells strongly expressed proliferating cell nuclear antigen(PCNA)and vimentin,indicating active cellular proliferation.The incidence of epithelium-like cells varied from 13.6%to 54.4%of glomeruli in 48-week-old SHRs,and from 5.1%to 18.0%of glomeruli in age-matched Wistar-Kyoto(WKY)rats(P<0.01).The linear regression analysis further confirmed an obvious correlation between the incidence of epithelium-like cells and the glomerular injury.Moreover,early intervention with telmisartan could dramatically attenuate the progression of epithelium-like cells growth.However,no significant effect of telmisartan on the established epithelium-like cells was observed.Taken together,we demonstrated the involvement of abnormal epithelium-like cells growth in glomerular injury during hypertensive nephropathy in SHRs,and firstly showed the positive effects of the anti-hypertensive drug on the progression of epithelium-like cells growth.
基金supported by the National Key Research and Development Program of China(2022YFD1300303,2021YFF1000602)National Natural Science Foundation of China(32472878)China Agriculture Research System(CARS-35-PIG)。
文摘Estrus represents a critical phase in the porcine reproductive cycle and relies on functional ovarian development and coordinated steroidogenesis.Granulosa cells(GCs)mediate these processes by secreting estradiol(E_(2))and progesterone(P_(4)),which are essential for follicular maturation and ovulatory competence.While circular RNAs(circRNAs)have been implicated in steroid hormone synthesis,their involvement in the regulation of gilt estrous remains unclear.In this study,circRNA sequencing was performed on ovarian tissues of estrus(ES)and non-estrus(NES)gilts,resulting in the identification of a novel circRNA,termed circular SHOC2 leucine rich repeat scaffold protein(circSHOC2),which exhibited marked up-regulation in ES ovaries.Functional assays demonstrated that circSHOC2 overexpression enhanced E_(2)and P_(4)synthesis and increased the protein levels of key steroidogenic enzymes.Mechanistic investigation revealed that circSHOC2 sponges miR-130b-5p.Silencing miR-130b-5p significantly enhanced E_(2)and P_(4)production,along with the up-regulation of steroidogenic proteins.Additionally,miR-130b-5p targeted ASH1-like histone lysine methyltransferase(ASH1L),while its overexpression significantly inhibited ASH1L.Cotransfection experiments revealed that ASH1L mitigated the inhibitory effects of miR-130b-5p on E_(2)and P_(4)synthesis in GCs.These findings establish a regulatory axis in which circSHOC2 modulates steroidogenic capacity in porcine GCs via the miR-130b-5p/ASH1L pathway,offering mechanistic insight into the molecular basis of gilt estrus and providing potential targets to enhance reproductive efficiency.
