Publications by Author: Weipu Mao

The activin-follistatin-inhibin (AFI) axis plays a crucial role in sexual development and reproduction. Recently it was demonstrated that these proteins are also synthesized by many local tissues and regulate different biological activities, including tissue regeneration and cancer metastasis. However, little is known about the expression profile of the AFI axis in the bladder and its role in bladder function and dysfunction. We have examined the expression profile of 11 AFI family members in the mouse bladder. INHA, INHBA, and follistatin are the major ligand subunits detected among the six examined in the bladder. ACVR1, ACVR1B, and ACVR2B are the major receptor subunits detected among the five examined in the bladder. Immunolocalization studies reveal unique cellular distributions of these ligands and receptors within the bladder. The urothelial-localized ACVR2B/ACVR1B receptor complex suggests a role of activin signaling in urothelial function. The stimulatory activin A is present only in a subset of interstitial cells, separated from the urothelial activin receptor ACVR2B/ACVR1B by a basement membrane containing accumulated inhibitory ligand FST and by a layer of activin-negative myofibroblasts. This spatial information on AFI signal molecules suggests that activin A-positive interstitial cells might regulate urothelial cell function via paracrine signaling through activin A-ACVR2B/ACVR1B interaction. Further analysis of the human bladder confirmed the expression profile of the AFI axis, and revealed significantly upregulated expression of INHBA-ACVR2B in bladder cancer. These data suggest roles for these molecules in the growth and metastasis of bladder cancer, and highlight their potential as diagnostic and prognostic biomarkers.

OBJECTIVES: To examine the impact of overactive bladder (OAB) on all-cause and cardiovascular mortality in women in a real-world setting, and to examine the association of TyG-related indices with OAB.

METHODS: Data on 6580 women aged ≥20 years were collected from the National Health and Nutrition Examination Survey (NHANES) database. Kaplan-Meier curves and Cox survival analysis were used to evaluate the association between OAB and all-cause and cardiovascular mortality. Biomarkers for metabolic syndrome were assessed for their association with OAB, including triglyceride-glucose (TyG) and TyG-related indices. The association between TyG-related indices and OAB was evaluated using restricted cubic splines (RCS), receiver operating characteristic (ROC) curves and multivariate logistic regression, with propensity score matching (PSM) employed to balance confounders between OAB and non-OAB groups.

RESULTS: Kaplan-Meier curves showed that OAB was associated with a poorer prognosis, and multivariate Cox regression analyses indicated that OAB was an independent risk factor for both all-cause and cardiovascular mortality. RCS revealed a positive association between TyG-related indices and OAB. Both ROC curves and multivariate logistic regression analysis indicated that TyG-WHtR (TyG combined with waist-to-height ratio) was strongly associated with OAB, with a higher TyG-WHtR associated with an increased risk of OAB. The retrospective design and selection bias may be the potential limitations.

CONCLUSIONS: OAB is positively associated with all-cause and cardiovascular mortality in women. TyG-related indices are positively associated with OAB, with TyG-WHtR as the most effective index.