TGR5 expression in normal kidney and renal neoplasms

Abstract

BackgroundThe G protein-coupled bile acid receptor (TGR5) is a cell surface receptor which induces the production of intracellular cAMP and promotes epithelial-mesenchymal transition in gastric cancer cell lines. TGR5 is found in a wide variety of tissues including the kidney. However, the patterns of TGR5 expression have not been well characterized in physiologic kidney or renal neoplasms. We explore the expression of TGR5 in benign renal tissue and renal neoplasms and assess its utility as a diagnostic marker.MethodsSixty-one renal cortical neoplasms from 2000 to 2014 were retrieved. TGR5 protein expression was examined by immunohistochemistry. TGR5 mRNA was also measured by real-time PCR.ResultsIn normal renal tissue, TGR5 was strongly positive in collecting ducts, distal convoluted tubules and thin loop of Henle. Proximal convoluted tubules showed absent or focal weak staining. In clear cell renal cell carcinomas (RCCs), 25 of 27 cases (92%) were negative for TGR5 (p < 0.001). TGR5 mRNA was also significantly decreased in clear cell RCCs, suggesting that decreased TGR5 protein expression may be attributable to the downregulation of TGR5 mRNA in these tumors. All 11 papillary RCCs expressed TGR5 with 45% (5/11) exhibiting moderate to strong staining. All chromophobe RCCs and oncocytomas were positive for TGR5 with weak to moderate staining. TGR5 mRNA expression in these tumors was similar to normal kidney. All urothelial carcinomas of the renal pelvis strongly expressed TGR5 including a poorly differentiated urothelial carcinoma with sarcomatoid features.ConclusionTGR5 is strongly expressed in collecting ducts, distal convoluted tubules and thin loop of Henle. TGR5 protein and mRNA expression were notably decreased in clear cell RCCs and may be helpful in differentiating these tumors from other RCCs.

The role of TGR5 as an onco-immunological biomarker in tumor staging and prognosis by encompassing the tumor microenvironment

“…Besides, we further found that a low expression of TGR5 also has better OS in GBM, KIRP, LGG, THYM, and UVM but a high expression related with better OS in CESC, MESO, SARC, and SKCM, which means that TGR5 may be an important indicator for predicting the prognosis of cancer patients. Besides, TGR5 also plays different roles in different tumors, which is also consistent with our research results ( 37 – 39 ). Our cellular experiments and TGR5 gene expression levels in skin cancer, osteosarcoma, and renal cell carcinoma have further validated the results.…”

“…The most important clinically and experimentally relevant finding has been investigated: the relationship between TGR5 and clinical outcome, particularly tumors ( 9 – 12 , 30 – 37 ). Whether TGR5 has a certain molecular mechanism in all TCGA tumors needs to be further clarified.…”

Renal Farnesoid X Receptor improves high fructose-induced salt-sensitive hypertension in mice by inhibiting DNM3 to promote nitro oxide production

“…TGR5 is a member of G-protein-coupled-receptor superfamily and activated by various bile acids, preferentially by LCA and DCA [18,24]. TGR5, strongly expressed in renal tubular cells and mesangial cells, is found to have beneficial effects in the kidney like FXR [28][29][30]. A recent study has demonstrated that FXR can stimulate TGR5 gene expression by a FXR responsive element [31].…”

Metabolite Sensing GPCRs: Promising Therapeutic Targets for Cancer Treatment?

“…Finally, TGR5 is aberrantly overexpressed in non-small cell lung cancer, where its activation promotes cell proliferation and migration through JAK2 and STAT3 pathway [141]. In the field of diagnosis, Zhao and colleagues propose the use of the specific reduction in GPBAR-1 observed in clear cell renal carcinomas, as a distinguishing factor from other malignant renal carcinomas such as papillary renal carcinoma cells (RCCs), chromophobe RCCs, collecting duct carcinomas or clear cell papillary RCCs [142].…”