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AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.
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Objective: To assess the expression of ajuba LIM protein (AJUBA) in oral squamous cell carcinoma (OSCC) and to determine its role in cell proliferation, migration, and invasion in OSCC. Methods: The expression of AJUBA at mRNA and protein levels in OSCC was determined by quantitative polymerase chain reaction (qPCR) and immunohistochemical approaches, respectively. This was fol-lowed by analysis of the correlations between AJUBA levels and clinicopathological features of OSCC. The effects of AJUBA on cell pro-liferation, migration, and invasion in OSCC were assessed by MTT, wound healing, and transwell migration assays, respectively. West-ern blot assays were performed to check for the potential regulation of the Snail/E-cadherin pathway by AJUBA. Results: The expres-sion of AJUBA was significantly higher in OSCC tissues compared to that in adjacent normal tissues and correlated with T stage, cell dif-ferentiation, lymph node metastasis, and recurrence in OSCC. Elevated AJUBA levels indicated poor prognosis in patients with OSCC. Depletion of AJUBA impaired cell proliferation, migration, and invasion abilities of OSCC cells. Data from Western blot assays showed that AJUBA facilitated the expression of Snail but inhibited that of E-cadherin. Conclusions: AJUBA is overexpressed in OSCC and may influence cell proliferation and invasion in OSCC by modulating the Snail/E-cadherin pathway.
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Ajuba was found in cell connections, and the subsequent studies showed that it can shuttle between the nucleus and cytoplasm for signals transmission. Under normal physiological conditions, Ajuba promotes cell proliferation and differentiation by regulating cell cycle and participating in signaling pathways. In addition, Ajuba is closely related to the development of various tumors, such as breast cancer, colorectal cancer, head and neck squamous cell carcinoma, etc. However, Ajuba functions as an oncogene or a tumor suppressor gene in different tumors. In carcinomas, Ajuba can also promote tumor cell proliferation and promote tumor invasion and metastasis by regulating epithelial-mesenchymal transition. Some progress has been made in the development of small molecular inhibitors or targeted drugs for Ajuba, and there are considerable therapeutic prospects.