Fifty-year habitat subdivision enhances soil microbial biomass and diversity across subtropical land-bridge islands.

Although habitat loss and subdivision are considered main causes of sharp declines in biodiversity, there is still great uncertainty concerning the response of soil microbial biomass, diversity, and assemblage to habitat subdivision at the regional scale. Here, we selected 61 subtropical land-bridge islands (with small, medium, and large land areas) with a 50-year history of habitat subdivision and 9 adjacent mainland sites to investigate how habitat subdivision-induced unequal-sized patches and isolation affects biomass, diversity, and assemblages of soil bacteria and fungi. We found that the soil bacterial and fungal biomass on all unequal-sized islands were higher than that on mainland, while soil bacterial and fungal richness on the medium-sized islands were higher than that on mainland and other-sized islands. The habitat subdivision-induced increases in microbial biomass or richness were mainly associated with the changes in subdivision-specified habitat heterogeneities, especial for soil pH and soil moisture. Habitat subdivision reduced soil bacterial dissimilarity on medium-sized islands but did not affect soil fungal dissimilarity on islands of any size. The habitat fragment-induced changes in soil microbial dissimilarity were mainly associated with microbial richness. In summary, our results based on the responses of soil microbial communities from subtropical land-bridge islands are not consistent with the island biogeographical hypotheses but are to some extent consistent with the tradeoff between competition and dispersal. These findings indicate that the response of soil microbial communities to habitat subdivision differed by degree of subdivision and strongly related to habitat heterogeneity, and the distribution of microbial diversity among islands is also affected by tradeoff between competition and dispersal.

Erratum: Tongxinluo inhibits neointimal formation by regulating the expression and post-translational modification of KLF5 in macrophages.

[This corrects the article on p. 4778 in vol. 8, PMID: 27904679.].

Tongxinluo inhibits neointimal formation by regulating the expression and post-translational modification of KLF5 in macrophages.

Neointimal hyperplasia is a common pathological characteristic in diverse vascular remodeling diseases. The inflammatory response that follows vascular injury plays an important role in intimal hyperplasia. Tongxinluo (TXL), a traditional Chinese medicine, can ameliorate neointimal formation via suppressing vascular inflammatory response induced by vascular injury. However, the mechanisms underlying anti-inflammatory and anti-intimal hyperplasia of TXL are still not fully understood. The aim of present study was to examine whether the expression and post-translational modification of KLF5 were involved in the vasoprotective effects of TXL. In vivo, TXL inhibited neointimal formation induced by carotid artery injury. In vitro, TNF-α treatment of macrophages resulted in the increased proliferation and migration, but the effects of TNF-α on macrophages were blocked by TXL treatment. Next, KLF5 expression was up-regulated by carotid artery injury in vivo, as well as by exposure of macrophages to TNF-α in vitro, whereas TXL treatment abrogated the up-regulation of KLF5 by TNF-α or vascular injury. Intimal hyperplasia was strongly reduced in macrophage-specific KLF5 knockout (KLF5ly-/-) mice, indicating that TXL inhibits intimal hyperplasia by suppression of KLF5 expression. Furthermore, besides down-regulating KLF5 expression in macrophages, TXL also regulated KLF5 stability by ubiquitination and sumoylation of KLF5. Finally, TNF-α induced KLF5 sumoylation via PI3K/Akt signaling, whereas TXL inhibited Akt phosphorylation induced by TNF-α. We conclude that the multiple ingredients in TXL may act on different targets, which in turn generates a range of actions that manifest as a comprehensively vasoprotective effect.

TMEM16A and myocardin form a positive feedback loop that is disrupted by KLF5 during Ang II-induced vascular remodeling.

The TMEM16A protein is an important component of Ca(2+)-dependent Cl(-) channels (CaCCs) in vascular smooth muscle cells. A recent study showed that TMEM16A inhibits angiotensin II-induced proliferation in rat basilar smooth muscle cells. However, whether and how TMEM16A is involved in vascular remodeling characterized by vascular smooth muscle cell proliferation remains largely unclear. In this study, luciferase reporter, Western blotting, and qRT-PCR assays were performed. The results suggested that myocardin promotes TMEM16A expression by forming a complex with serum response factor (SRF) on the TMEM16A promoter in human aortic smooth muscle cells (HASMCs). In turn, upregulated TMEM16A promotes expression of myocardin and vascular smooth muscle cell marker genes, thus forming a positive feedback loop that induces cell differentiation and inhibits cell proliferation. Angiotensin II inhibits TMEM16A expression via Krüppel-like factor 5 (KLF5) in cultured HASMCs. Moreover, in vivo experiments show that infusion of angiotensin II into mice causes a marked reduction in TMEM16A expression and vascular remodeling, and angiotensin II-induced effects are largely reversed in KLF5 null (KLF5(-/-)) mice. KLF5 competes with SRF to interact with myocardin, thereby limiting myocardin binding to SRF and the synergistic activation of the TMEM16A promoter by myocardin and SRF. Our studies demonstrated that angiotensin II induces KLF5 expression and facilitates KLF5 association with myocardin to disrupt the myocardin-SRF complex, subsequently leading to inhibition of TMEM16A transcription. Blocking the positive feedback loop between myocardin and TMEM16A may be a novel therapeutic approach for vascular remodeling.