Background Despite lack of clinical therapy in acute kidney injury (AKI) or its progression to chronic kidney disease (CKD), administration of growth factors shows great potential in the treatment of renal repair and further fibrosis. At early phase of AKI, administration of exogenous fibroblast growth factor 2 (FGF2) protects against renal injury by inhibition of mitochondrial damage and inflammatory response. Here, we investigated whether this treatment attenuates the long-term renal interstitial fibrosis induced by I/R injury. Methods Unilateral renal ischemia-reperfusion (I/R) with contralateral nephrectomy was utilized as an in vivo model for AKI and subsequent CKD. Rats were randomly divided into four groups: Sham-operation group, I/R group, I/R-FGF2 group and FGF2-3D group. These groups were monitored for up to 2 months. Serum creatinine, inflammatory response and renal histopathology changes were detected to evaluate the role of FGF2 in AKI and followed renal interstitial fibrosis. Moreover, the expression of vimentin, α-SMA, CD31 and CD34 were examined. Results Two months after I/R injury, the severity of renal interstitial fibrosis was significantly attenuated in both of I/R-FGF2 group and FGF2-3D group, compared with I/R group. The protective effects of FGF2 administration were associated with the reduction of high-mobility group box 1 (HMGB1) mediated inflammatory response, the inhibition of TGF-β1/Smads signaling induced epithelial-mesenchymal transition and the maintenance of peritubular capillary structure. Conclusions A single dose of exogenous FGF2 administration 1 hour or 3 days after reperfusion inhibited renal fibrogenesis and thus blocked the transition of AKI to CKD. Our findings provided novel insight into the role of FGF signaling in AKI to CKD progression and underscored potential of FGF based therapy for this devastating disease.
The immunity‐related GTPases (IRGs) belong to the interferon‐inducible GTPase protein family, which mediates cell autonomous and innate immunity response to intracellular pathogens. Yet, the cellular and physiological function of IRGC, a member of the IRG subfamily, has not been elucidated. Here, we show that testis‐specific IRGC is specifically and highly expressed in mature spermatozoa and is required for sperm motility. IRGC induction results in the clustering of lipid droplets and initiation of their physical contact with mitochondria. When examining clinical semen samples, IRGC expression is significantly lower in asthenozoospermia patients relative to healthy individuals. These unique effects of IRGC identify it as an important player in sperm motility, and show the potential of lipid metabolism‐targeting therapeutic intervention aimed at controlling asthenozoospermia.
Thyroid autoimmunity (TAI) triggered by genetic and epigenetic variation occurs mostly in women of reproductive age. TAI is described mainly by positivity of anti‐thyroid peroxidase antibody (TPO‐Ab) and/or thyroglobulin antibody (TG‐Ab). TPO‐Ab, but not TG‐Ab, was suggested to be associated with pregnancy outcome in euthyroid women undergoing assisted reproductive technology (ART), but their results are conflicting. This meta‐analysis was performed to decide whether the presence of TPO‐Ab—in a concentration dependent manner—correlates with the success of ART. A systematic literature search was performed in the PubMed, Web of Science, and EMBASE databases for relevant articles published from January 1999 to April 2022, and these studies focused on the effect of TAI on pregnancy outcomes of women who underwent in vitro fertilization, intracytoplasmic sperm injection and intrauterine insemination and met the inclusion criteria: (i) the studies were prospective or retrospective study; (ii) all patients undergoing ART were tested for thyroid‐related antibodies; (iii) the assessed ART outcomes included miscarriage rate (MR) or delivery rate (DR). The exclusion criteria were: (i) female congenital uterine malformation, chromosomal diseases and other infectious diseases; (ii) overt hypothyroidism or pre‐existing thyroid disease; (iii) thrombus tendency. We divided the included patients into three groups according to the TPO‐Ab threshold they defined: (i) TPO‐Ab (−), threshold <34 IU/mL; (ii) TPO‐Ab‐34, threshold >34 IU/mL; (iii) TPO‐Ab‐100, threshold >100 IU/mL. We then extracted necessary relevant data, including MR and DR. Egger's test was used to evaluate the risk of publication bias. This meta‐analysis included a total of 7 literatures involving 7466 patients with TAI (−) and 965 patients with TAI (+) and revealed that there was no significant difference between group TPO‐Ab‐34 and group TPO‐Ab (−) in MR [risk ratio (RR): 0.61 (0.35, 1.08), p = 0.09] and DR [RR: 0.97 (0.83, 1.13), p = 0.69]. By contrast, compared to TPO‐Ab (−) group, TPO‐Ab‐100 patients showed markedly higher MR [RR: 2.12 (1.52, 2.96), p = 0.0046], and lower DR [RR: 0.66 (0.49, 0.88), p < 0.0001] with high degree of statistical significance. This meta‐analysis suggests that, for euthyroid patients, high level of TPO‐Ab (>100 IU/mL) could adversely influence the pregnancy outcome of ART.
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